The protective effect of propylthiouracil against hepatotoxicity induced by chromium in adult mice.

Environmental and occupational exposure to chromium compounds, especially hexavalent chromium (Cr(VI)), is widely recognized as potentially hepatotoxic in humans and animals. Its toxicity is associated with overproduction of free radicals, which induces oxidative damage. This study focused on the possible protective effect of propylthiouracil (PTU) against potassium dichromate (K2Cr2O7). Female mice were divided into four groups (groups I-IV) with seven animals in each group. Group I served as a control, which received tap water; group II received K2Cr2O7 alone (75 mg kg(-1) body weight (b.w.)) via drinking water; group III received both K2Cr2O7 via drinking water and PTU by intramuscular injection at a dose 2.5 mg/100 g(-1) b.w. twice a week, and group IV received PTU alone twice a week for 30 days. Exposure of mice to Cr promoted oxidative stress with an increase in malondialdehyde, protein carbonyl, and advanced oxidation protein product levels. Nonenzymatic antioxidants such as glutathione, nonprotein thiol, vitamin C levels and enzymatic antioxidant activities such as glutathione peroxidase and superoxide dismutase were decreased, while catalase activity was increased. Biomarkers of liver injury such as aspartate and alanine transaminases, lactate dehydrogenase activities, bilirubin, albumin, and glucose levels were increased, while triglyceride and cholesterol levels decreased. Coadministration of PTU restored the above-mentioned parameters to near-normal values. The histological findings confirmed the biochemical results.

Fenthion, an organophosphorus pesticide, induces alterations in oxidant/antioxidant status and histopathological disorders in cerebrum and cerebellum of suckling rats.

Fenthion (FEN) is an organophosphorus pesticide known for its wide toxic manifestations. In this study, the effects of FEN were evaluated on the cerebrum and cerebellum oxidant/antioxidant status and histopathological disorders in the suckling rats. Pregnant rats were divided into two groups: control group received pure water, while FEN group received daily by their drinking water 551 ppm of FEN from the 14th day of pregnancy until day 14 after delivery. Acetylcholine esterase (AChE) activity was inhibited in both the cerebrum and cerebellum of suckling rats whose mothers were treated with FEN. The cerebrum and cerebellum oxidative damage was demonstrated by a significant increase of malondialdehyde (MDA), advanced oxidation protein product and glutathione (GSH) levels and disturbance in the antioxidant enzyme activities. A significant decline of non-protein thiol and vitamin C levels was also observed. These changes were confirmed by histopathological observations which were marked by pyknotic neurons in the cerebrum and apoptotic cells in the cerebellum of FEN-treated rats. In the cerebellum of FEN-treated rats, the most conspicuous damage was the absence of external granular layer, indicating growth retardation. These data suggested that exposure of pregnant and lactating rats to FEN induced oxidative stress and histopathological disorders in the cerebrum and cerebellum of their pups. Thus, the use of FEN must be under strict control, especially for pregnant and lactating mothers.

Effect of selenium on methimazole-induced liver damage and oxidative stress in adult rats and their offspring.

This study aimed to investigate the protective effect of selenium (Se) on methimazole (MMI; an antithyroid drug)-induced hepatotoxicity in adult rats and their progeny. Female Wistar rats were randomly divided into four groups of six rats in each group: group I served as controls that received standard diet; group II received MMI in drinking water as 250 mg L(-1) and standard diet; group III received both MMI (250 mg L(-1), orally) and Se (0.5 mg kg(-1) of diet); group IV received Se (0.5 mg kg(-1) of diet) as sodium selenite. Treatments were started from the 14th day of pregnancy until day 14 after delivery. Exposure of rats to MMI promoted oxidative stress with an increase in liver malondialdehyde levels, advanced oxidation protein products and protein carbonyl contents and a decrease in the levels of glutathione, nonprotein thiols and vitamin C. A decrease in the activities of liver glutathione peroxidase, superoxide dismutase, catalase and lactate dehydrogenase and in the levels of plasma total protein and albumin was also observed. Plasma transaminase activities and total, direct and indirect bilirubin levels increased. Coadministration of Se through diet improved all biochemical parameters. The histopathological changes confirmed the biochemical results. Therefore, our investigation revealed that Se, a trace element with antioxidant properties, was effective in preventing MMI-induced liver damage.

Dimethoate induces kidney dysfunction, disrupts membrane-bound ATPases and confers cytotoxicity through DNA damage. Protective effects of vitamin E and selenium.

Dimethoate (DM) is an organophosphate insecticide widely used in agriculture and industry and has toxic effects on non-target organisms especially mammalian. However, we still know little about DM-induced kidney injury and its alleviation by natural antioxidants. In the present study, selenium (Se), vitamin E, DM, Se+DM, vitamin E+DM, Se+vitamin E+DM were given to adult rats for 4 weeks. Plasma creatinine and uric acid, kidney MDA, PC, H2O2 and AOPP levels were higher, while Na(+)-K(+)-ATPase and LDH values were lower in the DM group than those of controls. A smear without ladder formation on agarose gel was shown in the DM group, indicating random DNA degradation and DM-induced genotoxicity. A decrease in kidney GSH, NPSH and plasma urea levels and an increase in GPx, SOD and catalase activities were observed in the DM group when compared to those of controls. Plasma cystatin C levels increased, indicating a decrease in glomerular filtration rate. When Se or vitamin E was added through diet, the biochemical parameters cited above were partially restored in Se+DM and vitamin E+DM than DM group. The joint effect of Se and vitamin E was more powerful against DM-induced oxidative stress and kidney dysfunction. The changes in biochemical parameters were substantiated by histological data. In conclusion, our results indicated a possible mechanism of DM-induced nephrotoxicity, where renal genotoxicity was noted, membrane-bound ATPases and plasma biomarkers were disturbed. Se and vitamin E ameliorated the toxic effects of this pesticide in renal tissue suggesting their role as potential antioxidants.

Protective effects of Artemisia campestris upon fenthion-induced nephrotoxicity in adult rats and their progeny.

The purpose of this study was to assess the possible protective effects of Artemisia campestris against fenthion-induced nephrotoxicity in adult rats and their progeny. Fenthion was administered orally at a dose of 551 ppm, which represented » of LD50, for 21 consecutive days to pregnant and lactating rats. Oxidative stress was monitored in the kidney by measuring malondialdehyde (MDA), GSH levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase activities (GPx). Fenthion caused a significant induction of oxidative damage in kidney as evidenced by increased MDA levels from 5.32 ± 0.47 nmol/100 mg tissue to 11.72 ± 0.83 nmol/100 mg tissue for pups and from 5.18 ± 0.45 nmol/100 mg tissue to 10.84 ± 1.67 nmol/100 mg tissue for dams (p < 0.001). A significant increase (p < 0.001) in the activities of SOD, CAT and GPx was observed. Co-administration of Artemisia c. at a dose of 5% (w/w) in the diet of fenthion-treated rats showed a significant reno-protection against fenthion-induced cytotoxic effects. It could be concluded that Artemisia c. is promising as a protective agent against nephrotoxicity during the exposure to fenthion.

Oxidative stress-related lung dysfunction by chromium(VI): alleviation by Citrus aurantium L.

Chromium(VI), a very strong oxidant, causes high cytotoxicity through oxidative stress in tissue systems. Our study investigated the potential ability of ethanolic Citrus aurantium L., family Rutaceae extract, used as a nutritional supplement, to alleviate lung oxidative damage induced by Cr(VI). A high-performance liquid chromatography coupled with a mass spectrometer method was developed to separate and identify flavonoids in C. aurantium L. Six flavonoids were identified, as (1) poncirin, (2) naringin, (3) naringenin, (4) quercetin, (5) isosinensetin, and (6) tetramethyl-o-isoscutellarein. Adult Wistar rats, used in this study, were divided into six groups of six animals each: group I served as controls which received standard diet, group II received via drinking water K2Cr2O7 alone (700 ppm), groups III and IV were pretreated for 10 days with ethanol extract of C. aurantium L. at doses of 100 and 300 mg/kg body weight/day, respectively, and then K2Cr2O7 was administrated during 3 weeks, and groups V and VI received during 10 days only C. aurantium L. ethanol extract at doses of 100 and 300 mg/kg/day, respectively. Ethanol extract of C. aurantium L. was administered orally. Rats exposed to Cr(VI) showed in lung an increase in malondialdehyde and protein carbonyl levels and a decrease in sulflydryl content, glutathione, nonprotein thiol, and vitamins C and E levels. Decreases in enzyme activities such as in Na(+)K(+) ATPase, catalase, glutathione peroxidase, and superoxide dismutase were noted. Pretreatment with C. aurantium L. of chromium-treated rats ameliorated all biochemical parameters. Lung histological studies confirmed the biochemical parameters and the beneficial role of C. aurantium L.

Protective effects of vitamin E and selenium against dimethoate-induced cardiotoxicity in vivo: biochemical and histological studies.

There is considerable interest in the study of free radical-mediated damage to biological systems due to pesticide exposure. However, there is a lack of consensus as to which determinations are best used to quantify future risks arising from xenobiotic exposure and natural antioxidant interventions. Our study investigated the potential ability of selenium and/or vitamin E, used as nutritional supplements, to alleviate cardiotoxicity induced by dimethoate. Female Wistar rats were exposed for 30 days either to dimethoate (0.2 g L⁻¹ of drinking water), dimethoate+selenium (0.5 mg kg⁻¹ of diet), dimethoate+vitamin E (100 mg kg⁻¹ of diet), or dimethoate+selenium+vitamin E. The exposure of rats to dimethoate promoted oxidative stress with a rise in malondialdehyde, advanced protein oxidation, and protein carbonyl levels. An increase of glutathione peroxidase, superoxide dismutase, and catalase activities was also noted. A fall in acetylcholinesterase and Na⁺ K⁺-ATPase activities, glutathione, nonprotein thiols, vitamins C and E levels was observed. Plasma levels of cholesterol, triglycerides, and low density lipoprotein-cholesterol increased and those of high density lipoprotein-cholesterol decreased. Coadministration of selenium or vitamin E to the diet of dimethoate-treated rats ameliorated the biochemical parameters cited above. The histopathological findings confirmed the biochemical results and the potential protective effects of selenium and vitamin E against cardiotoxicity induced by dimethoate.

Dimethoate induced oxidative damage and histopathological changes in lung of adult rats: modulatory effects of selenium and/or vitamin E.

OBJECTIVE: To determine the efficiency of selenium and/or vitamin E to alleviate lung oxidative damage induced by dimethoate, an organophosphorus compound. METHODS: Adult Wistar rats were exposed during 30 days either to dimethoate (0.2 g/L of drinking water), dimethoate+selenium (0.5 mg/kg of diet), dimethoate+vitamin E (100 mg/kg of diet), or dimethoate+selenium+vitamin E. RESULTS: Exposure to dimethoate caused oxidative stress in lung evidenced by an increase of malondialdehyde, protein carbonyl groups and advanced oxidation protein products. An increase in glutathione peroxidase, superoxide dismutase, catalase and a decrease in acetylcholinesterase and butyrylcholinesterase activities, glutathione, non-protein thiols and vitamins C levels were observed. Histopathological changes in lung tissue were noted as emphysema, hemorrhages and hemosiderin deposits. Co-administration of selenium or vitamin E to the diet of dimethoate treated rats ameliorated the biochemical parameters as well as histological impairments. The joint effect of these elements was more powerful in antagonizing dimethoate-induced lung oxidative damage. CONCLUSION: We concluded that selenium and vitamin E ameliorated the toxic effects of this pesticide in lung tissue suggesting their role as potential antioxidants.

Ameliorating effect of selenium on chromium (VI)-induced oxidative damage in the brain of adult rats.

Chromium is known for its wide toxic manifestations. This experiment aims to evaluate the effect of selenium against oxidative stress induced by chromium in the cerebrum and cerebellum. Female Wistar rats were randomly divided into four groups of six each: group I served as controls which received the standard diet; group II received drinking water K(2)Cr(2)O(7) alone (700 ppm); group III received both K(2)Cr(2)O(7) and Se (0.5 mg Na(2)SeO(3)/kg of diet); and group IV received Se (0.5 mg/kg of diet) for 3 weeks. The exposure of rats to K(2)Cr(2)O(7) promoted oxidative stress in the cerebrum and cerebellum with an increase in malondialdehyde and a decrease of nonenzymatic antioxidant levels such as glutathione, nonprotein thiol, and vitamin C. An increase of enzyme activities like catalase, glutathione peroxidase, and superoxide dismutase activities was also observed. Acetylcholinesterase activity was inhibited after treatment with K(2)Cr(2)O(7). Co-administration of Se restored the parameters cited above. The histopathological findings confirmed the biochemical results.

Dimethoate-induced oxidative damage in erythrocytes of female adult rats: possible protective effect of vitamin E and selenium supplemented to diet.

Pesticide hazards have been accentuated by the sharp rise in their agricultural, industrial and domestic use. Acute exposure to pesticides can cause oxidative damage. Our study investigated the potential ability of selenium (Se) and/or vitamin E, used as nutritional supplements, to alleviate erythrocyte oxidative damage induced by dimethoate (DM), an organophosphate pesticide. Female Wistar rats were exposed to DM (0.2g/L(-1) of drinking water), DM + Se (0.5 mg/kg of diet), DM + vitamin E (100 mg/kg of diet), or DM + Se + vitamin E. Rats exposed to DM for 30 days showed an increase in malondialdehyde levels, superoxide dismutase and glutathione peroxidase activities in their erythocytes, while Na(+),K(+)-ATPase and catalase activities, glutathione, non-protein thiol, vitamin E and vitamin C levels decreased. We also noted an increase in lactate dehydrogenase activity, marker of haemolysis and a decrease in acetylcholinesterase, the principal mode of organophosphorus action. Co-administration of Se or vitamin E to the diet of DM-treated rats ameliorated the biochemical parameters cited above. But the combined effect of Se and vitamin E was more powerful in antagonizing DM-induced oxidative stress. Therefore, our investigation revealed that both Se and vitamin E were useful elements in preventing DM-induced erythrocytes damage.

Oxidative damage in erythrocytes of adult rats and their suckling pups exposed to gibberellic acid.

Gibberellic acid (GA(3)) is a plant growth regulator used in agriculture worldwide. The present study investigated the propensity of GA(3) to induce hematological disorders. Pregnant Wistar rats were randomly divided into two groups: group I served as controls; group II received orally GA(3) (200 ppm) from the 14th day of pregnancy until day 14 after delivery. GA(3) reduced the number of red blood cells, hemoglobin concentration, and hematocrit in suckling rats, while these parameters remained unchanged in their mothers. White blood cells increased in mothers and were unchanged in their pups. Several studies have associated these hematological disorders with oxidative stress. In fact, GA(3) treatment revealed in erythrocytes a significant increase in malondialdehyde levels and a decrease in antioxidant enzyme activities such as superoxide dismutase, catalase, and glutathione peroxidase. Moreover, a significant decline was observed in acetylcholinesterase activity, glutathione, nonprotein thiols, and vitamin C levels.

Oxidative stress induced by 2,4-phenoxyacetic acid in liver of female rats and their progeny: biochemical and histopathological studies.

The 2,4-Dichlorophenoxyacetic acid (2,4-D) was used in agriculture as an herbicide in many countries including Tunisia. The aim of this study was to evaluate the effects of 2,4-D on liver function of adult rats and their progeny. Female Wistar rats were divided into two groups: the controls and the treated rats which received 600 ppm of 2,4-D in their drinking water from the 14th day of pregnancy until day 14 after delivery. In 2,4-D group, a significant decrease in body weight of pups was noted, when compared to controls. Liver antioxidant enzyme activities, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) decreased, while malondialdehyde (MDA) levels increased in dams and pups. Moreover, plasma aminotransferases (ALT, AST), gamma glutamil transpeptidase (GGT), lactate dehydrogenase (LDH), bilirubin and albumin levels were increased significantly. The biochemical modifications were correlated with histopathological studies. We concluded that 2,4-D induced hepatotoxicity in adult and suckling rats.

Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny.

The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl(2) in drinking water; group 3 received 350 ppm CoCl(2) in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity. Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.

Neurotoxicity and oxidative stress induced by gibberellic acid in rats during late pregnancy and early postnatal periods: biochemical and histological changes.

Gibberellic acid (GA(3)) is an endogenous plant growth regulator used worldwide in agriculture; however, little is known about its biochemical and physiological effects on mammals. This study investigated possible neurotoxic effects of GA(3) on the cerebrum and cerebellum of suckling rats. Female Wistar rats were given daily 200 ppm GA(3) in drinking water from the 14th day of pregnancy until day 14 after delivery. Acetylcholinesterase activity in both cerebellum and cerebrum was inhibited after treatment with GA(3). Neurotoxicity was demonstrated by a significant increase in malondialdehyde level and a decrease in the antioxidant enzyme activities of catalase, superoxide dismutase, glutathione peroxidase in the cerebrum and cerebellum of suckling pups. A significant decline of glutathione content and vitamin C was also observed. The biochemical parameters were correlated histologically with an abnormal development of the external granular layer and a loss of Purkinje cells in the cerebellum of GA(3)-treated suckling rats.

Toxicity of methimazole on femoral bone in suckling rats: alleviation by selenium.

AIMS: Selenium has a pharmacological properties and it is well considered as an antioxidant. The present study investigated the potential ability of selenium, used as a nutritional supplement, to alleviate bone impairments in suckling rats whose mothers were treated with methimazole, an antithyroid drug. MAIN METHODS: Female Wistar rats were randomly divided into four groups of six each: group I served as control which received standard diet; group II were rendered hypothyroid by administration of methimazole (250 mg L(-1) in their drinking water); group III received both methimazole (250 mg L(-1) in their drinking water) and selenium (0.5 mg kg(-1) of diet); group IV received 0.5 Na(2)SeO(3) mg kg(-1) of diet. Treatments were started from the 14th day of pregnancy until day 14 after delivery. KEY FINDINGS: Methimazole treatment decreased femur length and weight in 14-day-old rats, when compared to controls. Femur antioxidant enzyme activities, superoxide dismutase, catalase and glutathione peroxidase decreased. Lipid peroxidation recorded an increase revealed by high femur malondialdehyde levels. Methimazole also caused a significant decrease in calcium and phosphorus levels in bone. Yet, in plasma and urine, they increased and decreased inversely. Besides, plasma total tartrate-resistant acid phosphatase was enhanced, while total alkaline phosphatase was reduced. Co-administration of selenium through diet improved the biochemical parameters cited above. Nevertheless, distorted histoarchitecture revealed in hypothyroid rat femur was alleviated by Se treatment. SIGNIFICANCE: The present study suggests that selenium is an important protective element that may be used as a dietary supplement protecting against bone impairments.

Oxidative stress and thyroid impairment after gibberellic acid treatment in pregnant and lactating rats and their offspring.

Gibberellic acid (GA3) has been worldwide used in agriculture as a plant growth regulator. The purpose of this study is to assess the effects of GA3 on the morphology and the thyroid hormone levels in adult rats and their suckling pups. Animals were given daily 200 ppm GA3 in drinking water from the 14th day of pregnancy until day 14 after delivery. Compared with a control group, GA3-treated mothers and pups showed an increase in body and thyroid weights, a decrease in plasma FT4 and FT3 levels, which were more pronounced in pups than in their mothers. Thyroid iodine content was also decreased in pups. These biochemical modifications corresponded histologically; the majority of follicles had cubical epithelial cells, which surrounded empty vesicular cavities. Toxicity was objectified by a significant increase in plasma malondialdehyde, protein carbonyls, and advanced oxidation protein products levels in GA3-treated dams and their suckling pups; while, the activities of superoxide dismutase, catalase, and glutathione peroxidase were decreased in plasma of both dams and their pups. Moreover, a significant decline was observed in plasma glutathione, nonprotein thiols, and vitamin C levels. We conclude that GA3 treatment affects thyroid function and plasma antioxidant status in adult rats and their progeny.

2,4-Dichlorophenoxyacetic acid effects on nephrotoxicity in rats during late pregnancy and early postnatal periods.

2,4-Dichlorophenoxyacetic acid (2,4-D) is largely used as a selective herbicide in Tunisia. The purpose of this study was to investigate the effects of 2,4-D on the kidneys of adult rats and their suckling pups. Female Wistar rats were divided into two groups: the controls and the treated rats that received 600 mg/L of 2,4-D in their drinking water from the 14th day of pregnancy until day 14 after delivery. Exposure to 2,4-D induced nephrotoxicity as evidenced by an increase in thiobarbituric acid reactive substances and protein carbonyl levels and a decrease in antioxidant enzyme activities such as catalase, superoxide dismutase, glutathione peroxidase in the kidneys of suckling pups and their mothers. In addition, a significant decline in kidney glutathione, non-protein thiol and vitamin C levels was also observed. Histological changes, seen in the kidney of mothers and their pups treated with 2,4-D are characterized by a narrowed Bowman's space, tubular epithelial cells degeneration, widened tubular lumen and vascular congestion.

Oxidative damage induced by chromium (VI) in rat erythrocytes: protective effect of selenium.

Excess chromium (Cr) exposure is associated with various pathological conditions including hematological dysfunction. The generation of oxidative stress is one of the plausible mechanisms behind Cr-induced cellular deteriorations. The efficacy of selenium (Se) to combat Cr-induced oxidative damage in the erythrocytes of adult rats was investigated in the current study. Female Wistar rats were randomly divided into four groups of six each: group I served as controls which received standard diet, group II received in drinking water K(2)Cr(2)O(7) alone (700 ppm), group III received both K(2)Cr(2)O(7) and Se (0.5 Na(2)SeO(3) mg/kg of diet), and group IV received Se (0.5 mg/kg of diet) for 3 weeks. Rats exposed to K(2)Cr(2)O(7) showed an increase of malondialdehyde and protein carbonyl levels and a decrease of sulfhydryl content, glutathione, non-protein thiol, and vitamin C levels. A decrease of enzyme activities like catalase, glutathione peroxidase, and superoxide dismutase activities was also noted. Co-administration of Se with K(2)Cr(2)O(7) restored the parameters cited above to near-normal values. Therefore, our investigation revealed that Se was a useful element preventing K(2)Cr(2)O(7)-induced erythrocyte damages.

Oxidative stress induced by chromium (VI) in bone of suckling rats.

Exposure to hexavalent chromium Cr(VI) compounds is of concern in many Cr-related industries and their surrounding environments. K(2)Cr(2)O(7) is widely recognized as an animal and human carcinogen, mutagen, and teratogen. The present study investigated the bone maturity of suckling rats whose mothers were treated with K(2)Cr(2)O(7). Experiments were carried out on female Wistar rats given 700 ppm of K(2)Cr(2)O(7) in their drinking water from the 14th day of pregnancy until day 14 after delivery. Exposing dams to K(2)Cr(2)O(7) caused disorders in the bone of their progeny. As corollary to this, malondialdehyde levels increased, while glutathione, a non-protein thiol and vitamin C decreased. Alteration of the antioxidant system in the treated group was also confirmed by the significant decline of superoxide dismutase, catalase, and glutathione peroxidase activities. Furthermore, K(2)Cr(2)O(7) induced changes in bone mineralization, especially calcium and phosphorus levels, which decreased. Whereas, in plasma and urine, they increased and decreased inversely. These results suggest that K(2)Cr(2)O(7) accelerated bone resorption activity. In fact, in treated pups, total tartrate-resistant acid phosphatase, which reflected bone resorption, was enhanced while total alkaline phosphatase, which reflected bone formation, was reduced. The impairment of bone function was corresponded histologically.

Oxidative stress induced by gibberellic acid on kidney tissue of female rats and their progeny: biochemical and histopathological studies.

Gibberellic acid (GA(3)) is an endogenous plant growth regulator used worldwide in agriculture. The objective of this study was to investigate the effects of GA(3) on the kidney function of adult rats and their pups. Female Wistar rats were given daily 200 ppm GA(3) in drinking water from the 14th day of pregnancy until day 14 after delivery. GA(3) induced nephrotoxicity, as evidenced by a reduction in the 24-h urine volume and an increase in plasma creatinine, urea and uric acid levels. Nephrotoxicity was objectified by a significant increase of malondialdehyde level and a decrease of antioxidant enzyme activities like catalase, superoxide dismutase, glutathione peroxidase and glutathione content in kidneys of suckling pups and their mothers. Kidney histological studies confirmed biochemical parameters. We concluded that the exposure of rats to GA(3) induced oxidative stress and histopathological changes in kidneys of suckling rats and their mothers during late pregnancy and early postnatal periods.