Effects of sodium fluoride on hepatic toxicity in adult mice and their suckling pups

In this investigation, we have evaluated the effect of sodium fluoride (NaF) on hepatic function in pregnant and lactating mice and their suckling pups. Experiments were carried out on female Wistar mice given 500 ppm sodium fluoride (226 ppm fluoride ion) in their drinking water from the 15th day of pregnancy until day 14 after delivery. All mice were sacrificed on day 14 after parturition. Our results showed a significant decrease in serum levels of total protein and albumin, a marked hypoglycaemia and a significant decline in serum cholesterol and triglyceride levels in fluoride-treated mice and their pups. Whereas globulin and biluribin levels in serum were not significantly changed by NaF treatment. On the other hand, serum transaminase activities (aspartate transaminase; alanine transaminase), which well known as markers of liver function, were elevated indicating hepatic cells’ damage after treatment with fluoride. Lipid peroxidation increased in NaF-treated mice and pups, as revealed by high liver malondialdehyde levels, while serum total antioxidant status showed a significant decline. These biochemical modifications in NaF-treated mice also correspond histologically with extensive ballooning, hepatocellular necrosis and infiltration of mononuclear cells. These effects were not observed in controls.     

Fluoride-induced brain damages in suckling mice

In order to reveal mechanisms of brain damages resulted from fluoride toxicity, we treated adult female mice of Swiss Albinos strain by 500 ppm NaF (226 ppm F⁻) in their drinking water from the 15th day of pregnancy until the day 14 after delivery. All mice were sacrificed on day 14 after parturition. During treatment, levels of thiobarbituric acid reactive substances (TBARS), the marker of lipid peroxidation extend, increased, while the activities of the antioxidant enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), and the level of glutathione (tGSH) decreased significantly in both cerebellum and cerebrum compared with those of the control group. These results suggested that fluoride enhanced oxidative stress in the brain, thereby disturbing the antioxidant defense of nursing pups. In addition, acetylcholinesterase (AChE) activity in both cerebellum and cerebrum was inhibited after treatment with fluoride. In our previous studies we have found, a decrease in plasma thyroid hormone levels of nursing pups whose mothers were treated by NaF. In cerebellum of mice, migration of neurons from the external granular layer to the internal granular layer occurred postnatally and was dependent upon the presence of thyroid hormone. In hypothyroidism, several neurons failed to complete their migration and died. Key guidance signals to these migrating neurons were provided by laminin, an extracellular matrix protein fixed to the surface of astrocytes. In the present study we examined the expression and distribution of laminin in cerebellum of 14-day-old mice. Immunoreactive laminin was disappeared by postnatal day 14 in cerebellum parenchyma of control pups and was restricted to vasculature despite the continued presence of granular cells in the external granular layer. In contrast, in cerebellum of NaF treated pups, laminin was deposited in organised punctuate clusters in the molecular layer. These data indicated that the disruption of laminin distribution might play a major role in the profound derangement of neuronal migration observed in cerebellum of NaF treated pups.     

Dose-dependent sub-chronic toxicity of diethyl phthalate in female Swiss mice

The experiment was conducted to study the after effects of administering DEP at different doses to female Swiss mice for a period of 90 days. Group I mice were fed on normal diet and water ad libitum. Group II mice were maintained on normal diet mixed with corn oil at 8.25 mg/kg of the diet/day as oil control. Group III, IV and V mice were given diethyl phthalate dissolved in corn oil mixed with the diet at 10, 25 and 50 mg/kg of the diet/day, which is approximately equal to 1.25, 3.125 and 6.25 mg/kg body weight/day. A significant dose dependent increase was observed in serum acid phosphatase (ACP) whereas, serum and liver triglycerides levels showed a significant increase only in the high-dose treated group. Significant dose-dependent increase in serum aspartate and alanine aminotransferase (AST and ALT) and liver glycogen was observed. Serum lactate dehydrogenase (LDH) was significantly increased only in 25 and 50 ppm DEP-treated mice. Liver cholesterol was significantly increased in all the treated groups. Liver histology by light microscopy showed intracellular vacuolations in all the treated groups which was much more evident in the 25 and 50 ppm DEP-treated mice while hepatocellular degeneration and hypertrophy of the hepatocytes was evident in 50 ppm DEP-treated mice. Proliferation of mitochondria and peroxisomes was evident in the electron micrographs of the 10 ppm DEP-treated mice while 25 and 50 ppm DEP-treated mice showed increase in lipid droplets and severe mitochondrial proliferation.     

Evaluation of propolis effects on some biochemical parameters in rats treated with sodium fluoride

The present study in which 42 female rats, each weighing 200−250 g, were used covered a period of 21 days. The animals were divided into six groups. The first group served as the control group, whereas Group 2 was administered propolis at a dose of 200 mg/kg/bw in drinking water for 21 days. Group 3 was first provided with normal drinking water for a period of 14 days, and was subsequently administered propolis at a dose of 200 mg/kg/bw in drinking water for 7 days. Group 4 was first given normal drinking water for 14 days, and was secondly administered 100 ppm fluoride as a sodium fluoride in drinking water for 7 days. Group 5 was first administered propolis alone at a dose of 200 mg/kg/bw in drinking water for 14 days, and was secondly administered 100 ppm fluoride in association with 200 mg/kg/bw propolis for 7 days. Finally, Group 6 was first provided with normal drinking water for 14 days, and was secondly administered 100 ppm fluoride in association 200 mg/kg/bw propolis for a period of 7 days. At the end of the 21st day, blood samples were collected from the heart of each animal into both heparinised tubes and tubes without anticoagulants. Glucose, triglyceride, cholesterol, total protein, and uric acid levels, and aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities in the serum, as well as malondialdehyde (MDA) levels, glutathione peroxidase (GSH-Px) in the plasma, erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities were measured. When compared to the control group, statistical differences were determined to exist with respect to oxidative stress parameters which involved increase in MDA levels in Groups 4−6, decrease in SOD activity in Groups 4 and 6, increase in CAT activity in Groups 5 and 6, and decrease in GSH-Px activity in Groups 4 and 6. Furthermore, in comparison to the control group, significant differences were observed with respect to certain serum biochemical parameters, including decrease in glucose levels in Groups 5 and 6, decrease in triglyceride levels in Groups 2 and 4, decrease in cholesterol levels in Groups 2 and 5, decrease in the total protein level of Groups 4−6, decrease in the ALT activity of Groups 5 and 6, increase in the AST activity of Group 4, decrease in the ALP activity of Groups 2−6 and increase in the uric acid level of Group 2. In the groups that were administered propolis in association with fluoride, improvement was observed in some oxidative stress parameters and certain other biochemical parameters. Changes determined in the oxidative stress parameters (especially MDA and SOD) were indicative of the anti-radical activity of propolis on the free radicals generated by sodium fluoride. However, the values not drawing completely close to those of the control group can be explained with propolis not being able to completely eliminate the free radicals and the other adverse effects generated by fluoride.     

The in vivo effect of mirex on soluble hepatic enzymes in the rat

Adult male and female rats fed dietary mirex in concentrations of 10, 20, 30, 40, and 50 ppm for 4 weeks exhibited significant decreases in liver levels of lactic dehydrogenase, malic dehydrogenase, sorbitol dehydrogenase, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase as compared to control levels. Enzyme losses were cytoplasmic and decreased in magnitude with increased time of exposure and dietary mirex concentrations. Serum sorbitol dehydrogenase levels were increased above control levels during the first week of mirex exposure while hepatic sorbitol dehydrogenase levels were concomitantly decreased below the control levels. Hepatic glutamic oxaloacetic transaminase levels were significantly decreased during the first week for all dietary mirex concentrations as were the other enzymes at the 40 and 50 ppm mirex concentrations. The magnitude of the enzyme decreases in female rat tissue was consistently lower than enzyme decreases in the male rat tissue fed equivalent dietary mirex dosages. Liver weights for male rats increased significantly at all dietary mirex levels during week one. However, only animals receiving the 40 and 50 ppm dietary mirex levels showed significant liver weight increases at the end of week 4. Female rat liver weights were increased at the 30 and 40 ppm mirex dietary levels after 4 weeks. No significant differences in body weights were observed for any dietary level of mirex. Mirex hepatic residues appeared to be equal for both sexes. No gross histological alterations were observed following treatment.     

The effects of deltamethrin on some serum biochemical parameters in mice

Sixty white male mice were used in this study. Three groups, each comprising 20 mice were established. The control group (Group 1) was provided ad libitum pellet feed. On the other hand, the experimental groups, namely, Groups 2 and 3 were given pellet feed containing deltamethrin throughout the day, so that the animals were administered doses of 7.5 and 30 mg/kg/body weight/day, respectively. Blood samples were collected from all groups on the 15th, 30th, 45th, and 60th days of the experiment for measurement of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alcaline phosphatase (ALP), amylase and cholinesterase activities, and levels of glucose, urea, creatinine, triglyceride, cholesterol, calcium, phosphor, sodium, potassium, and chloride. According to data obtained, on the 15th day of the study, compared to the control group, statistically significant increase in urea, cholesterol, ALP, cholinesterase, calcium, and potassium levels/activities, and significant decrease in SGOT activity and chloride levels in Group 2, and significant increase in cholesterol, ALP, cholinesterase, calcium, potassium and chloride levels/activities in Group 3, and significant decrease in SGOT activity in Group 3 were determined. On the 30th day of the study, in comparison to the control group, triglyceride and cholesterol levels and ALP activity were determined to be significantly increased in the Group 2, whereas SGOT activity were significantly reduced in Group 2, and triglyceride and cholesterol levels were demonstrated to be significantly increased and SGOT activity was significantly reduced in Group 3. On the 45th day of the study, compared to the controls, significant increase in cholesterol and sodium levels, and significant decrease in triglyceride levels and ALP activity in Group 2, significant increase in creatinine, cholesterol and sodium levels and cholinesterase activity, and significant decrease in glucose, SGPT, ALP and phosphor levels/activities were detected in Group 3. On the 60th day, in other words, in the last period of the study, ALP activity, and triglyceride, calcium, and phosphor levels were determined to be significantly increased and significant decrease in amylase activity in Group 2. Furthermore, significant increase in triglyceride, ALP, amylase, calcium, phosphor, and potassium levels/activities, and significant decrease in glucose and creatinine levels were observed in Group 3. However no correlation was determined to exist between the changes were found to be statistically significant, and the administration dose and duration of deltamethrin in all periods and groups.     

Metabolism and toxicity of metribuzin in mouse liver

Metribuzin was hepatotoxic in mice when administered intraperitoneally (ip) at sublethal doses of 150 to 250 mg/kg. Four dose-dependent abnormalities were evident. Histopathological examination revealed a fulminant centrilobular hepatic necrosis. The serum glutamic-pyruvic transaminase (GPT) activity was elevated. The liver glutathione (GSH) content was almost completely depleted. There was extensive covalent binding of radiocarbon from [carbonyl-¹⁴C]metribuzin to liver proteins and also high blood levels of metribuzin fragments. Each of these four effects of metribuzin on the liver or blood was alleviated or blocked in mice pretreated with piperonyl butoxide (PB), which inhibits the cytochrome P-450-dependent monooxygenase. PB also reduced the lethality of metribuzin by three-fold. In contrast, pretreatment with diethyl maleate to suppress the liver GSH content increased the lethality of metribuzin by twofold. The hepatotoxicity and acute lethality of metribuzin were probably due to reactive intermediates which are normally detoxified by GSH conjugation. The principal urinary metabolites of metribuzin in mice and rats are mercapturic acids, which arise via metribuzin sulfoxide or deaminometribuzin sulfoxide reacting with GSH. Sulfoxidation therefore appears to activate metribuzin to an electrophilic metabolite which, in the absence of GSH, binds to tissue proteins producing hepatotoxicity.     

Fenthion induced-oxidative stress in the liver of adult rats and their progeny: Alleviation by Artemisia campestris

Fenthion (FEN) is an organophosphate insecticide used in both agricultural and urban areas throughout the world including Tunisia. Recent investigations have proved the crucial role of natural antioxidants to prevent the damage caused by toxic compounds. In this study, we investigated the role of Artemisia campestris (Ac) leaf powder in protection against oxidative damage and hepatotoxicity induced by fenthion in female rats and their pups. Female Wistar rats were divided into four groups: group I served as controls which received standard diet, group II received orally FEN 551 ppm, group III received both 551 ppm of FEN and experimental diet (5% Artemisia) and group IV received experimental diet (5% Artemisia). Oral administration 551 ppm of FEN by drinking water to adult rats caused hepatotoxicity as monitored by the increase in the levels of hepatic markers enzymes (transaminases and lactate dehydrogenase), total cholesterol (TC) and triglycerides (TG), as well as hepatic malondialdehyde (MDA) levels thus causing a drastic alteration in antioxidant defence system. Particularly, the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the level of reduced glutathione (GSH) increased by FEN. These biochemical alterations were accompanied by histological changes marked by leucocytes infiltration, sinusoidal dilatation (moderate peliosis), granuloma inflammatory disorders and necrosis in hepatocytes of dams. While, slight leucocytes infiltration was shown in pups. Treatment with Ac prevented the liver damage induced by FEN, as revealed by inhibition of hepatic lipid peroxidation accompanied by an improvement of liver histopathological changes, CAT and GPx activities except GSH and SOD which were not modified. It could be concluded that A. campestris is promising a protective agent against hepatotoxicity during the exposure to fenthion.     

Adrenalectomy and the adaptive liver response in mirex-treated rats

Mirex, an organochlorine compound, was administered as a single oral dose (100 mg/kg body wt) to both intact and adrenalectomized juvenile male Sprague-Dawley rats. Both mirex-treated intact and adrenalectomized animals (dosed 24 hr postsurgery) exhibited significant increases in liver weight to body weight ratios compared to controls. However, the liver weight to body weight ratios in mirex-treated intact animals were significantly greater than those observed in mirextreated adrenalectomized animals. Significant increases were observed in liver weight to body weight ratios in adrenalectomized animals treated with mirex 4 days after surgery. However, the 96-hr mortality in mirex-treated adrenalectomized animals increased from 20% (mirex dose given 1 day postadrenalectomy) to 56% (mirex dose given 4 days postadrenalectomy). Mirex treatment of intact and adrenalectomized animals had no significant effect upon either serum or hepatic activities of glutamic oxalacetic transminase, glutamic pyruvic transaminase, sorbitol dehydrogenase, or protein concentrations. Bromsulfophthalein clearance also was not affected by mirex treatment in adrenalectomized animals. Serum glucose concentrations were significantly decreased in both intact and adrenalectomized animals by mirex treatment. Daily corticosterone supplements to adrenalectomized animals restored liver hypertrophy and serum glucose concentrations to levels observed in mirex-treated intact animals. These results suggest that mirex-induced liver enlargement may be mediated by corticosterone.     

Amelioratory effect of vitamin E on organophosphorus insecticide diazinon-induced oxidative stress in mice liver

Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of organophosphate insecticides (OPIs), the aim of this study was to investigate the ameliorative properties of vitamin E (vitE) against the subchronic effect of diazinon (DZN) on oxidative damage markers such as lipid peroxidation (LPO) and the antioxidant defense system (ADS) in the liver of male MFI albino mice. The groups were intraperitoneally (i.p) administered with either vehicle or vitE (100 mg/kg body weight) or ¼ LD₅₀ of DZN (16.25 mg/kg b.w.) or ½ LD₅₀ of DZN; 32.5 mg/kg b.w) or ¼ LD₅₀-DZN + vitE or ½ LD₅₀ + vitE every consecutive day for 14 days. Hepatic damage markers analysis revealed that alanine transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly decreased in both DZN doses. Also, the significantly increased levels of biomarkers of oxidative stress as LPO and protein carbonyl (PC) and the decreased antioxidant defenses like reduced glutathione (GSH), and free radical scavenger enzymes viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rx) were noted in DZN-treated groups as compared to control group. Distinctly lower levels of GSH and increased levels of LPO, along with alterations in endogenous antioxidant enzymes were evident in hepatic toxicity of DZN which is dose-dependent. Hepatic specific marker enzymes were restored to normalcy in mice supplemented with vitE following treatment with DZN which otherwise was decreased in the DZN-treated mice. The results show that co-treatment of vitE with DZN prevents or diminishes the oxidative stress of DZN-treated mice and may act as a putative protective agent against DZN-induced liver tissue injury.     

Nephrotoxicity induced by dimethoate in adult rats and their suckling pups

The purpose of this study was to investigate the effect of dimethoate (DM), an organophosphorus insecticide, on oxidative stress in kidneys of adult rats and their suckling pups. Female Wistar rats were given daily DM in drinking water 0.2 g/L equivalent to 40 mg/kg bw from day zero until day 10 after delivery. A significant increase was found in relative kidney weights of treated adult rats and their offspring. DM administration affected strongly specific markers of kidney function such as the 24-h urine volume which was higher than in the controls. In test group we have found higher plasma levels and lower urinary levels of creatinine, a specific indicator of glomerular function, and urea than in the controls. Significant increase in creatinine clearance was also found in treated mothers and their suckling pups. These results indicated that DM exposure provoked low glomerular filtration rate in treated group. Interestingly, these biochemical modifications were accompanied by a marked enhancement of lipid peroxidation in kidney indicating significant induction of oxidative damage and alterations of enzymatic antioxidant defences in test group. Impairment of renal function corresponds histologically. In fact, histological changes, seen in the kidney of mothers and their pups treated with DM are characterized by a narrowed Bowman’s space, degenerative of tubular epithelial cells and widened tubular lumen. Moreover in mothers, extensive vascular congestion was observed.We concluded that the effect of DM treatment in lactation period of mothers was fairly reflected in the offspring in all parameters analysed.     

Botanical pesticide, azadirachtin attenuates blood electrolytes of a freshwater catfish Heteropneustes fossilis

The present study was aimed to investigate the effects of purified neem extract azadirachtin on the blood electrolytes of Heteropneustes fossilis for short- and long-term. In short-term exposure the fish were subjected to 0.8 (i.e. 80%) of 96 h LC₅₀ value of azadirachtin (41.89 mg L⁻¹) for 96 h. In long-term exposure the experiment was performed for 28 days by using 0.2 (i.e. 20%) of 96 h LC₅₀ value of azadirachtin (10.47 mg L⁻¹). Fish were sacrificed (anaesthesized with MS 222) from control and experimental (azadirachtin) groups after 24, 48, 72, and 96 h in short-term exposure and after 7, 14, 21, and 28 days in long-term experiment. Blood samples were analyzed for calcium and inorganic phosphate levels. Acute exposure of azadirachtin caused a progressive decrease in the serum calcium levels after 48 h in fish H. fossilis which persists till the close of the experiment (96 h). The serum inorganic phosphate levels remained unaffected till 72 h in the azadirachtin exposed fish. After 96 h the levels exhibit a decrease. Chronic azadirachtin treatment caused a decrease in serum calcium levels at day 14. This decrease continued till the end of the experiment. The serum phosphate level of the azadirachtin treated fish decreased on day 14 and 21. However, on day 28 the levels were close to the normal values.     

Biochemical and histological hepatic changes of Nile tilapia Oreochromis niloticus exposed to carbaryl

The purpose of this study was to evaluate biochemical and morphological responses induced by carbaryl in the liver of Nile tilapia (Oreochromis niloticus) exposed during 21 days to sublethal concentrations (0.25 and 0.5 mg L⁻¹), testing also recover for 14 days in clean water, after 14 days exposure. The activities of the following enzymes were measured: superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR), and reduced (GSH) and oxidized glutathione (GSSG). Globally, our data showed that exposure to carbaryl decreased the SOD, CAT, GR, and GST activities, except for the SOD and GST activities after 14 days exposure to 0.25 mg L⁻¹. In contrast, after 14 days exposure the GR activity of the hepatic tissue from carbaryl-treated fish showed significant elevation in relation to the control. When fish were left to recover, a positive response was seen in the GSH and GSSG contents. The results of the recovery group suggest that the toxicity produced by carbaryl is reversible to some extent within 15 days. The liver histological analysis showed differences between fish concerning the cellular vacuolization degree (VD) of the hepatocytes. In fish exposed to carbaryl it was observed an increasing hepatocellular basophilia. No other histological alterations were observed when fish was exposed to carbaryl, except a few necrotic foci at day 7. The sections stained with PAS reaction showed that the vacuolization was always not due to glycogen deposits, thus suggesting lipid accumulation. The combined increased basophilia and glycogen depletion is a common, although non-specific, liver response to many toxicants. In short, this work shows a relation between histological and biochemical changes in liver and carbaryl exposure. The effects of carbaryl were observed at different concentrations.     

Biochemical alteration induced by monocrotophos in the blood plasma of fish, Channa punctatus (Bloch)

Monocrotophos (MCP), commonly known as azodrin, is one of the organophosphate (OP) pesticides extensively used in agricultural practices throughout the world. Channa punctatus were exposed to sublethal concentrations (0.96 and 1.86 mg/L) of monocrotophos for 15 and 60 days to assess the alterations in the level of some biochemical parameters in blood plasma. Significant alterations in all the biochemical parameters were found to be dose dependent. Hypoglycemia and hypocholesteremia were observed in plasma of fish at both exposure periods (15 and 60 days). Increased activities of glutamate-oxalacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), acid and alkaline phosphatase of blood plasma indicated hepatic tissue damage. Decrease in lactate dehydrogenase (LDH) content in plasma further indicated lower metabolic rate after 60 days of exposure. Significant decline in triglycerides content was observed in fish exposed to both sublethal concentrations of monocrotophos. We suggest that analysis of biochemical parameters in the fish blood may be useful in environmental biomonitoring.     

A two generation chronic mixture toxicity study of Clophen A60 and diethyl phthalate after gestational and lactational exposure in female Wistar rats

Polychlorinated biphenyls and diethyl phthalate are both lipophilic in nature and are likely to be present in the same environmental compartment or bioaccumalate over a period of time, thus a mixture toxicity study was undertaken to evaluate the type of interaction between polychlorinated biphenyls (Clophen A60) and diethyl phthalate over two generations in female Wistar rats. Healthy male and female albino rats of Wistar strain weighing 75-100 g (6-7 weeks old) were randomly assigned to four groups of six each. Group I male and female rats were fed on normal diet and water ad libitum. Group II male and female rats were maintained on normal diet mixed with corn oil as oil control. GroupS III and IV male and female rats were given Clophen A60 and diethyl phthalate dissolved in corn oil mixed with the diet at 50 mg/kg of the diet individually to each group. Group V male and female rats received a mixture of diethyl phthalate and Clophen A60, each dissolved in corn oil mixed with the diet at 50 mg/kg of the diet. Hundred days after the treatment, females were mated with the males in each group for 10 days. Exposure to diethyl phthalate and Clophen A60 was continued throughout mating, gestation until termination at weaning, which was 150 days of total treatment period of the parental generation female rats. Treatment for F1 generation male and female pups (6 males & 6 females) with Clophen A60 and diethyl phthalate individually and in mixture was continued at doses reduced to 25 mg/kg of the diet after they reached 75-100 g in weight. The treatment was carried out similar to the parental generation for a period of 150 days. Liver and serum aspartate aminotransferase, liver cholesterol and glycogen were significantly increased in the F1 generation Clophen A60 + diethyl phthalate treated group, whereas serum cholesterol, liver glutathione and glutathione reductase showed a significant decrease in the F1 generation Clophen A60 + diethyl phthalate treated group as compared to the parental generation mixture and individually treated groups as well as the individually treated F1 generation groups. A significant increase was observed in the liver and serum aspartate aminotransferase activity of Clophen A60 and serum aspartate aminotransferase levels of diethyl phthalate treated F1 generation rats as compared to the parental generation Clophen A60 and diethyl phthalate individually and mixture treated rats. Liver glutathione levels were significantly decreased in the F1 generation Clophen A60 and diethyl phthalate individually treated rats which was similar to the parental generation individually treated rats as compared to the controls. Liver glutathione reductase level was also significantly declined in the diethyl phthalate treated F1 individual group as compared to diethyl phthalate individually treated parental generation rats. Histology of the liver showed fatty degeneration in the mixture treated F1 generation rats as compared to Clophen A60 and diethyl phthalate individually treated F1 rats and parental generation Clophen A60 and diethyl phthalate individually and mixture treated rats. Thus, in spite of dose reduction and continuous exposure over two generation’s to a mixture of diethyl phthalate and Clophen A60 exposed through gestation, lactation and diet leads to a synergistic toxic effect in the F1 generation.     

Prallethrin induced serum biochemical changes in Wistar rats

The present study was designed as a repeated dose 28-day oral toxicity study in rodent. All the rats were randomly divided into five groups (C1, C2, T1, T2 and T3) each containing 10 Wistar rats (5 male and 5 female). Group C1 served as control as no treatment was administered. Group C2 was administered groundnut oil (1 ml/100 g b.wt) and served as vehicle control. Group T1 was put on high dose 153.33 mg/kg b.wt (LD50/3), while group T2 received intermediate dose of 92 mg/kg b.wt (LD50/5), and group T3 was administered low dose of 46 mg/kg b.wt (LD50/10) of Prallethrin suspended in 1 ml/100 g b.wt of groundnut oil. Blood samples were collected from all groups on the 7th, 14th, 21st and 28th day of the experiment for measurement of serum glucose, serum urea, serum triglyceride, serum cholesterol, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) and serum alkaline phosphatase (ALP). According to data obtained on the 7th day of the study, no statistically significant change in any of the treatment groups was observed as compared to the control group. On the 14th day of the study, in comparison to the control group, triglyceride level and ALP activity were found to be significantly increased in the group T1 female and group T1 male rats respectively. On the 21st day of the study, compared to the controls, significant increase in cholesterol and ALP levels were present in both T1 and T2 females and in addition to this total protein and triglycerides levels were also significantly increased in group T1 female rats. In group T1 male total protein, triglycerides, ALT and ALP activity was found to be increased significantly as compared to healthy control group. On the 28th day, all the recorded biochemical parameters were found to be significantly increased, except BUN and AST in group T1 female rats. In group T2 female rats, significantly increased cholesterol, ALT and ALP levels were observed. In group T3 female rats, none of the parameters were found to be significantly affected. Among male rats, only total protein level was found to be increased in groups T2 and T3. Whereas, total protein, triglyceride, ALT and ALP were significantly elevated in group T1 male rats at the end of the study. In conclusion, the results of this study demonstrate that subacute oral administration of Prallethrin; at dose levels of 1/3 LD50 and 1/5 LD50 for 28 days induces moderate toxic effects on different biochemical parameters.     

Effects of dimethoate (O,O-dimethyl S-methyl carbamoyl methyl phosphorodithioate) and Ethanol in antioxidant status of liver and kidney of experimental mice

Organophosphorus insecticides and ethanol individually cause free radical production induced by oxidative stress and alter the antioxidants and scavengers of free radicals. The present study indicates the effect caused by dimethoate in combination with ethanol on antioxidant status in mice. Daily, dimethoate at a dose of 18 mg/kg body weight and ethanol at 1 g/kg body weight were orally administered concurrently in a subacute study for 14 days. After the experimental period, the liver and kidney homogenates were analysed for various antioxidant enzymes. The results compared with dimethoate alone treated control indicated an increase in hepatic cytochrome P450 and lipid peroxidation. Decrease in superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and glutathione in liver was observed. In kidney, decrease in CAT, SOD, GR, GST, and GSH was observed. Acetyl cholinesterase activity of RBC was increased. No significant change was observed in catalase in liver and glutathione peroxidase in kidney. The results of the study allow us to hypothesize that dimethoate along with ethanol disturbs the antioxidant status.     

Fate of endosulfan in rats and toxicological considerations of apolar metabolites

[¹⁴C]Endosulfan, α or β isomers separately, was administered to rats as a single oral dose and as a dietary supplement for 14 days. No appreciable differences were observed in the fate of the two isomers. Five days after the single dose, 75% of the dose had been voided in the feces and 13% in the urine. Of the total radiocarbon consumed in the diet after 14 days, 56% had been eliminated in the feces and 8% in the urine. Bile collection studies showed that up to 47% of a single oral dose was eliminated from the liver via this route; enterohepatic circulation was not apparent. Maximum [¹⁴C]endosulfan equivalents in body tissue occurred in the kidney and liver, 3 and 1 ppm, respectively, after 14 days of feeding 5 ppm of endosulfan. Apolar metabolites in the excreta and/or tissues were a minor portion of the total residues and consisted of the sulfate, diol, α-hydroxy ether, lactone, and ether derivatives of endosulfan. The sulfate was slightly more toxic to mice than endosulfan, while the other products were less toxic. Neither endosulfan nor its metabolites were active in the Salmonella mutagenicity test. Endosulfan in the diet of rats for 28 days at 50 ppm did not induce liver oxidase enzymes, alter liver or kidney weights, or influence the rate of weight gain of the animals.