Effects of aluminum sulphate and citric acid ingestion on lipid peroxidation and on activities of superoxide dismutase and catalase in cerebral hemisphere and liver of developing young chicks

Effect of oral administration of aluminum sulphate (200 and 400 mg/kg body wt/day) without or with citric acid (62 mg/kg body wt/day) to day-old White Leghorn male chicks (n = 5 per group) for 30 days was studied on the activities of superoxide dismutase (SOD) and catalase, and level of lipid peroxidation in cerebral hemisphere and liver. A 400 mg dose of Al in the presence of citric acid inhibited cytosolic total and CN^--sensitive superoxide dismutase activities of the cerebral hemisphere in 7- and 30-day treated chicks, whereas in 15-day treated chicks the enzyme activities were decreased in response to both doses in the presence of citric acid. In case of liver, activities of these enzymes significantly decreased after 7, 15 and 30 days of treatment with 200 and 400 mg Al together with citric acid, whereas 400 mg Al alone inhibited the enzyme activities after 15 and 30 days of treatment. Cerebral catalase activity decreased in response to 400 mg Al when the chicks were also fed with citric acid for 7 and 30 days, but in 15-day treated chicks the enzyme activity was depleted following treatment with 200 and 400 mg Al combined with citric acid. 400 mg Al treatment for 7 days in combination with citric acid inhibited hepatic catalase activity and extension of the treatment period to 15 and 30 days also produced reduction in its activity even in response to the lower Al dose mixed with citric acid. CN^--insensitive SOD activity of cerebral hemisphere and liver was unaffected by Al. Al also failed to induce lipid peroxidation in both the tissues throughout the course of exposure. Activities of SOD and catalase of cerebral hemisphere and liver of 30-day old chicks were observed to be inhibited by in vitro incubation with different concentrations of Al. Our in vivo study demonstrates that only CN^--sensitive SOD is susceptible to Al. Further, responses of SOD and catalase to Al is tissue specific. The observed inhibition of antioxidant enzyme activities by A1 is suggestive of a prooxidant state. Induction of such an oxidative condition of the tissues may be attributed to a direct effect of the metal on enzyme molecules or in their synthesis.     

Toxicity of endosulfan on kidney of male rats in relation to drug metabolizing enzymes and microsomal lipid peroxidation

Endosulfan administration (po, 15 and 30 days at 7.5 and 10 mg/kg body wt respectively) inhibited the activity of microsomal mixed function oxidases in kidney tissue of male rats. Microsomal and cytosolic protein contents of kidney were significantly increased following 30 days endosulfan exposures. Profound induction in the activity profiles of alcohol dehydrogenase and cytosolic glutathione s-transferase was noticed, however, no such change was apparent in the activity of aldehyde dehydrogenase. Microsomal preparations from treated animals showed a dose and duration dependent increase in spontaneous lipid peroxidation. The observed biochemical changes persisted even after 7 days normalcy allowance provided after the endosulfan (10 mg/kg body wt) withdrawl. The results suggest a substantial renal toxicity of endosulfan to male rats in relation to microsomal mixed function oxidases and associated functions which possibly resulted from lipid peroxidative damage of microsomal membrane in treated animals.     

Acid proteolytic activities in mouse liver and muscle tissues after treatment with protease inhibitor leupeptin

The activities of acid proteolytic enzymes were assayed in the liver and muscular tissues of mice (Mus musculus) 1, 6 and 24 hr after the administration of a protease inhibitor leupeptin (i.p., 15.5 mg/kg body wt). Leupeptin administration induced a strong inhibition of cathepsin B and a moderate inhibition of cathepsin C and acid autolytic rate in mouse liver 1 hr after injection. Thereafter the inhibition reduced and disappeared during 24 hr. The activity of cathepsin D was increased in liver 6 and 24 hr after injection. The activity of beta-glucuronidase was not affected by the leupeptin treatment. The administration of leupeptin did not affect the rate of acid autolysis and the activities of cathepsin C and D in cardiac and skeletal muscles. A slight increase in cathepsin B activity was observed 1 hr after leupeptin treatment in calf muscles. The cause of both tissue and enzyme specific changes after leupeptin treatment is discussed.     

Effects of safrole and isosafrole pretreatment on N- and ring-hydroxylation of 2-acetamidofluorene by the rat and hamster

1. The effects of safrole and isosafrole pretreatment on both N- and ring-hydroxylation of 2-acetamidofluorene were studied in male rats and hamsters. 2. Isosafrole (100mg/day per kg body wt.) pretreatment of rats for 3 days did not have any effect on urinary excretion of hydroxy metabolites of 2-acetamidofluorene. However, similar pretreatment with safrole produced increased urinary excretion of N-, 3- and 5-hydroxy derivatives. 3. Similar treatment with these two chemicals for 3 days increased ring-hydroxylation activity by rat liver microsomal material. Increases in N-hydroxylation were much less than those in ring-hydroxylation. Isosafrole was twice as effective as safrole. 4. Increases in hydroxylating activity due to safrole or isosafrole treatment were inhibited by simultaneous administration of ethionine. Similarly, ethionine inhibition was almost completely reversed by the simultaneous administration of methionine. 5. Safrole or isosafrole (0.1mm and 1mm) inhibited 7-hydroxylation activity by liver microsomal material from control rats. At 1mm these two chemicals inhibited both 5- and 7-hydroxylation activity by liver microsomal material from 3-methylcholanthrene-pretreated rats. 3-Hydroxylation activity was not inhibited by 1mm concentrations of these two chemicals. 6. A single injection of safrole (50100 or 200mg/kg body wt.) 24h before assay had no appreciable effect on either N- or ring-hydroxylation activity by hamster liver microsomal material. However, isosafrole (200mg/kg body wt.) treatment inhibited N-, 3- and 5-hydroxylation activities by hamster liver microsomal material; it had no effect on 7-hydroxylation activity.     

Effects of nicotine and vitamin E on carbonic anhydrase activity in some rat tissues in vivo and in vitro

Effects of nicotine, nicotine + vitamin E and nicotine + Hippophea rhamnoides L. extract (HRe-1) on muscle, heart, lungs, testicle, kidney, stomach, brain and liver carbonic anhydrase (CA; EC 4.2.1.1.) enzyme activities were investigated in vivo. Groups of rats were given nicotine (0.5 mg/kg/day, i.p.), nicotine + vitamin E (75 mg/kg/day, i.g.), nicotine + HRe-1 (250 mg/kg/day, i.g.) and a control group vehicle only. The results showed that nicotine inhibited the heart, lung, stomach and liver CA enzyme activities by approximately 80% (p < 0.001), approximately 94% (p < 0.001), approximately 47% (p < 0.001) and approximately 81% (p < 0.001) respectively, and activated muscle and kidney, but had no effects on the testicle and brain CA activities. Nicotine + vitamin E inhibited the heart and liver CA enzyme activities by approximately 50% (p < 0.001), and approximately 50% (p < 0.001), respectively, and nicotine + vitamin E activated the muscle CA activity. However, nicotine + vitamin E had no effect on lung, testicle, kidney, stomach and brain CA activities. Nicotine + HRe-1 inhibited the heart and stomach CA enzyme activities by approximately 51% (p < 0.001), and approximately 32% (p < 0.002), respectively, and activated the muscle and brain CA activities, but had no effects on the lung, testicle, kidney, and liver CA activities. In vitro CA inhibition results for similar experiments correlated well with the in vivo experimental results in lungs, testicles, kidney, stomach, brain and liver tissues.     

Response of hepatic carbohydrate and cyclic AMP metabolism to cadmium treatment in rats.

Daily intraperitoneal injection of cadmium chloride (0.25 or 1 mg/kg) for 21 or 45 days into rats significantly stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-diphosphatase, and glucose-6-phosphatase, increased the concentrations of glucose and urea in the blood, and decreased the levels of glycogen in the liver. Whereas chronic cadmium treatment failed to alter adenosine-3',5'-monophosphate phosphodiesterase (phosphodiesterase) activity, the endogenous levels of cyclic AMP (cAMP) and the activity of basal- and fluoride-stimulated forms of hepatic adenylate cyclase (AC) were markedly increased in cadmium-injected animals. Treatment with the higher dose (1.0 mg/kg) of cadmium chloride for 45 days produced greater metabolic alterations in hepatic tissue than those seen with the lower dose (0.25 mg/kg) given for a shorter period of time (21 days). Discontinuation of cadmium administration for 14 days in rats previously injected with cadmium chloride (1 mg/kg per day) for 21 days, failed to reverse the observed changes in hepatic cAMP or carbohydrate metabolism. A similar persistence of metabolic alterations was noted in rats treated with cadmium (1 mg/kg per day) for 45 days and subsequently maintained without additional treatment for 28 days. Administration of an acute dose of cadmium chloride (60 mg/kg) decreased hepatic phosphodiesterase activity and glycogen content 1 h after the injection. In addition, acute cadmium exposure increased blood glucose, serum urea, and hepatic cAMP levels, and produced an augmentation of basal- and fluoride-activated AC. However, the activities of various hepatic gluconeogenic enzymes remained unaffected in animals given an acute dose of cadmium chloride (60 mg/kg). Data provide evidence that suggests that the gluconeogenic potential of liver is markedly enhanced following chronic exposure to cadmium and that the cadmium-induced changes in carbohydrate metabolism may be associated with an enhanced synthesis of cAMP. In addition, the present study shows that the cadmium-induced metabolic alterations persist even after the cessation of cadmium treatment for a period of 28 days.     

In vivo effects of cadmium on calmodulin and calmodulin regulated enzymes in rat brain.

Effect of chronic cadmium (Cd) exposure and the influence of diethyldithiocarbamate (DDC) on Cd absorption was studied on the brain of young male Wistar rats. A significant amount of Cd accumulated in cerebral cortices of rats after 4 weeks of Cd (6 mg/kg body wt) exposure (through gastric intubation). The biological activity of calmodulin (CaM) decreased significantly (p less than 0.001) in the cerebral cortices of these animals in comparison to the control group. 3'-5' Phosphodiesterase and synaptic membrane Ca(2+)-Mg(2+) ATPase were also significantly affected (p less than 0.01 and p less than 0.001 respectively). However, Cd treatment did not alter synaptic membrane adenylate cyclase activity and DDC (9.2 mg/kg body wt, intraperitoneal) treatment along with Cd (6 mg/kg body wt) enhanced Cd accumulation in cerebral cortices of treated animals resulting in an increased inhibition of CaM and CaM dependent enzymes. These data suggest that Cd may be acting via binding to CaM and uncoupling it from its normal cellular control of calcium.     

Effect of chlorpyrifos on thiobarbituric acid reactive substances, scavenging enzymes and glutathione in rat tissues

The present study showed that exposure of chlorpyrifos, O,O'-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothionate (CPF), a widely used pesticide in rats caused significant inhibition of acetylcholinesterase (AChE) activity in different tissues viz., liver, kidney and spleen. CPF exposure also generated oxidative stress in the body, as evidenced by increase in thiobarbituric acid reactive substances (TBARS), decrease in the levels of superoxide scavenging enzymes viz., superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in liver, kidney and spleen at all doses. Malondialdehyde levels were increased by 14%, 31% and 76% in liver, 11%, 31% and 64% in kidney and 32%, 75% and 99.9% in spleen when 50 mg, 100 mg and 200 mg/kg body wt. CPF was administered for three days. SOD and CAT activities were decreased in liver, kidney and spleen, while GPx activity showed slight increase in kidney at 50 mg and 100 mg dose, and decreased on further increase in dose of CPF. Liver and spleen showed dose-dependent decrease in GPx activity. The levels of reduced glutathione (GSH) was decreased, while oxidized glutathione (GSSG) was increased, thus a marked fall in GSH/GSSG ratio was observed in all tissues. A maximum decrease of 83% was observed in liver, followed by kidney and spleen, which showed 78% and 57% decrease, respectively in group given 200 mg/kg CPF. The levels of glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) were also decreased in liver and kidney, while spleen showed increase at lower doses, but decrease at high dose of CPF. The data provide evidence for induction of oxidative stress on CPF exposure.     

Effects of HgCl2 on porphobilinogen-synthase (E.C. 4.2.1.24) activity and on mercury levels in rats exposed during different precocious periods of postnatal life

Porphobilinogen-synthase (PBG-synthase) is an enzyme extensively used as a bioindicator of metals and other oxidizing agents. The objective of this study was to verify the effects of HgCl(2) (5mg/kg/day, s.c.), a metal that mainly affects the nervous and renal systems, on kidney, liver and brain from rats exposed during one of the phases considered critical for development. Mercury decreased PBG-synthase activity from liver, kidney and brain and altered corporal, renal and cerebral weights. The kidney was the most sensitive tissue. It accumulated a large amount of metal and PBG-synthase activity was decreased up to 50%. The second period seemed to be the most sensitive, because in this phase the rats presented alterations in body, brain and kidney weights, and there was also an expressive inhibition in hepatic and renal PBG-synthase activities. In general, large quantities of metal accumulated in the tissues are in agreement with the inhibition verified in these tissues.     

Effect of cadmium on tissue glutathione and glutathione peroxidase in rats: influence of selenium supplementation.

Administration of cadmium (2.5 mg/kg, sc on alternate days for 3 weeks) to male albino rats led to significant accumulation of cadmium and metallothionein in the liver and kidneys. The activity of glutathione peroxidase was significantly decreased whereas, the concentration of glutathione was increased in these organs. Glycine-l-14C incorporation studies showed enhanced synthesis of glutathione in kidney but not in the liver. Selenium supplementation (1 mg/kg/day orally) failed to prevent these cadmium-induced changes, although it resulted in very high accumulation of selenium in these organs indicating the formation of cadmium-selenium complex.     

Chemical sterilization of males - successful inhibition of spermatogenesis in langurs (Presbytis entellus entellus dufresne) after metopiron (SU-4885, Ciba) administration.

1. Daily administration of metopiron (SU-4885, Ciba) (10 mg/kg body wt. for 30 days) produced a massive atrophy of the spermatogenic elements. The pachytene primary spermatocytes have been implicated as the main site of damage. Seminiferous and Leydig cell shrinkage was conspicuous. Epididymal and vesicula seminalis structure and functions were severely affected. 2. RNA, protein and sialic acid contents of the testes, epididymides and seminal vesicles were reduced, whereas testicular cholesterol and enzyme phosphatase were elevated. 3. Marked reduction in the testicular glycogen was noticed. 4. Normal functioning of liver, kidney and general metabolic activities was revealed by clinical parameters (serum, transaminases, phosphatases, lipids, serum bilirubin, blood sugar and blood urea). Serum protein levels were low, whereas the serum cholesterol was elevated. 5. In conclusion: Metopiron (SU-4885, Ciba) at 10 mg/kg body wt. dose level did not cause severe damage to the vital organs but it produced an effective inhibition of spermatogenesis in male Presbytis in 30 days and thus induces an antifertility state.     

In vivo effects of 3-methylcholanthrene, phenobarbital, pyrethrum and 2,4,5-T isooctylester on liver, lung and kidney microsomal mixed-function oxidase system of guinea-pig: a comparative study

The optimum conditions (pH, microsomal protein amount and substrate concentration) of guinea-pig liver, lung and kidney microsomal aniline 4-hydroxylase, ethylmorphine N-demethylase and benzo[a]pyrene hydroxylase activities were determined. Male guinea-pigs weighing 500-700 g were administered 3-methylcholanthrene (25 mg/kg, i.p. 3 days), phenobarbital (75 mg/kg, i.p. 3 days), pyrethrum (120 mg/kg, i.p. 2 days) and 2,4,5-T isooctylester (200 mg/kg, i.p. 3 days). 3-Methylcholanthrene treatment caused significant increases in liver microsomal benzo[a]pyrene hydroxylase and kidney microsomal aniline 4-hydroxylase activities. However, with phenobarbital treatment the only significant increase was observed in liver microsomal ethylmorphine N-demethylase activity. Pyrethrum treatment decreased kidney microsomal ethylmorphine N-demethylase activity significantly. 2,4,5-T isooctylester treatment increased liver microsomal aniline 4-hydroxylase and lung microsomal ethylmorphine N-demethylase activities significantly. Liver microsomal NADPH-cytochrome c reductase activity was increased significantly by phenobarbital and pyrethrum treatment. The other treatments did not cause any significant changes in microsomal NADPH-cytochrome c reductase activities of liver, lung and kidney. Cytochrome P-450 content of guinea-pig liver microsomes were increased significantly about 2.5-fold and 2-fold by treatment with 3-methylcholanthrene and phenobarbital, respectively. 3-Methylcholanthrene also caused 1 nm spectral shift in the absorption maxima of CO difference spectrum of the dithionite-reduced liver microsomal cytochrome P-450, forming P-449.     

Hepatic effects of ketoconazole in the male Swiss Webster mouse: temporal changes in drug metabolic parameters

There have been conflicting observations regarding the effects of ketoconazole on hepatic metabolism. The objectives of these studies were to determine whether ketoconazole was an enzyme inducer or inhibitor in the mouse and then to establish the time frame of these ketoconazole-induced enzyme changes. Ketoconazole was administered (150 mg/kg p.o. X 4 days) to male Swiss Webster mice. Biochemical observations over a period of 6 days following treatment indicated that ketoconazole had a temporal biphasic effect on the liver. Although liver weight and microsomal protein were elevated, all other parameters monitored were lower at 2 h following ketoconazole treatment. At 24 h after the last dose of ketoconazole, hepatic biochemical parameters (liver wt., % liver wt./body wt., microsomal protein, and cytochrome P-450) were statistically elevated, while enzyme activities (benzphetamine N-demethylation, 6 beta- and 7 alpha-hydroxylation of testosterone, formation of androstenedione and UDP-glucuronyltransferase) were inhibited. At 72 h the ketoconazole-induced changes in the hepatic biochemical parameters were comparable to those observed at 24 h, and enzymatic parameters generally appeared to be induced by ketoconazole, with the exception of benzphetamine N-demethylase and UDP-glucuronyltransferase, which exhibited lower enzyme activities. Ethoxyresorufin O-deethylase, 7 alpha-hydroxylation of testosterone and glutathione S-transferase, on the other hand, were unaltered by ketoconazole treatment. The opposing effects of ketoconazole on benzphetamine N-demethylase and ethylmorphine N-demethylase at 72 h were further examined. Enzyme kinetics studies indicated that ketoconazole did not effect the Michaelis constants (Km) of the two substrates, but the maximum velocity (Vmax) of the reactions was altered.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simvastatin Treatment Ameliorates Injury of Rat Testes Induced by Cadmium Toxicity

Cadmium-induced testicular toxicity is mediated through oxidative stress and inflammation which eventually lead to cell death. Simvastatin, the antihyperlipidemic agent, exhibits additional antioxidant and anti-inflammatory activities. The aim of the present work was to investigate the protective effect of simvastatin against cadmium-induced testicular toxicity in rats. The rats received a single intraperitoneal (i.p.) injection of cadmium chloride (2 mg/kg). Simvastatin treatment (5 mg/kg/day, i.p.) was applied for three consecutive days, starting 1 day before cadmium administration. Cadmium significantly decreased serum testosterone, and testicular reduced glutathione and catalase activity, and significantly increased testicular malondialdehyde, nitric oxide, and cadmium ion levels. Simvastatin significantly ameliorated the biochemical changes induced by cadmium. Cadmium-induced testicular tissue injury observed by histopathological examination was attenuated by simvastatin. In addition, simvastatin significantly decreased the expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, nuclear factor-κB, and caspase-3, and increased heme oxygenase-1 expression in testicular tissue of rats exposed to cadmium toxicity. It was concluded that simvastatin, through its antioxidant and anti-inflammatory activities, provided a significant protective effect against cadmium-induced testicular toxicity in rats. However, starting treatment with simvastatin before cadmium exposure, as done in the present work, is not clinically applicable. Therefore, other investigations are needed to assess the protective effect of simvastatin treatment following induction of cadmium testicular toxicity.     

Induction of lipid peroxidation in hamster organs by the carcinogen cadmium: melioration by melatonin

Cadmium is a well-known human carcinogen. Lipid peroxidation is involved in cadmium-related toxicity and carcinogenesis. Melatonin is an effective antioxidant and free radical scavenger. The potential protective effects of melatonin against cadmium-induced lipid peroxidation in hamster brain, heart, kidney, testes, lung, and liver were examined. Lipid peroxidation was induced by intraperitoneal injection of cadmium chloride [single dose of 1 mg/kg body weight (bw)]. To test whether melatonin would protect against the toxicity of the carcinogen, the melatonin was injected peritoneally at a dose of either 15 mg/kg bw or 5 mg/kg bw, 0.5 h before cadmium treatment and thereafter at 8 h intervals during the day in the 48 h interval following the cadmium injection. One group of hamsters received only a single melatonin injection (a dose of 15 mg/kg bw, 30 min prior to cadmium). Forty-eight hours after cadmium injection, lipid peroxidation increased in brain, heart, kidney, testes, and lung. Either multiple injections of melatonin at both the 5 and 15 mg/kg bw doses, or a single injection of 15 mg/kg bw, prevented the cadmium-related increases in lipid peroxidation in brain, heart and lung. Cadmium-induced lipid peroxidation in kidney was prevented by melatonin when it was given as a single dose of 15 mg/kg bw. Melatonin slightly, but not significantly, reduced cadmium-induced lipid peroxidation in testes. It is concluded that cadmium toxicity, at least with regard to the resulting lipid peroxidation, is reduced by administering melatonin. This revised version was published online in July 2006 with corrections to the Cover Date.     

Alterations in isoforms of glutathione S-transferase in liver and kidney of cadmium exposed rhesus monkeys: Purification and kinetic characterization

Exposure of animals to cadmium (Cd) (25 mg kg-1 body wt day-1) for 10 weeks resulted in preferential accumulation of the metal in liver and kidney. Cd accumulation concomitantly increased zinc (Zn) concentration in both the organs. However, significant decrease in copper level was observed in liver, whereas kidney showed increase in copper (Cu) level. Cd exposure resulted in decreased total GST activity in liver (63%) and kidney (41%) as compared to control group monkeys on normal diet (group I). On isoelectric focusing (IFP) control liver GST segregated into thirteen isoenzymes, while in Cd-treated experimental animals (group II) liver GST resolved into nine isoenzymes. Similarly kidney GST from control animals separated into seven isoenzymes as compared to four isoenzymes from Cd-treated animals. Kinetic analysis showed that Cd exposure did not alter the affinity constant (Km) of GST for GSH and CDNB whereas maximal velocity (Vmax) for these substrates decreased as compared to controls in both the organs, indicating inhibition in GST synthesis by Cd. Cd resulted in a noncompetitive type of inhibition with respect to GSH in vitro. On isoelectric focussing GST of liver and kidney in group II resolved into nine and four isoenzymes as compared to thirteen and seven in group I, showing loss of four basic isoenzymes in case of liver and three isoenzymes in case of kidney. Monkey liver and kidney expressed all the three classes of GST isoenzymes i.e. , µ and , which were serologically identical to human , µ and GSTs. (Mol Cell Biochem 166: 55-63, 1997)     

Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats

Free radicals and oxidative stress have been implicated in the etiology of diabetes and its complications. This in vivo study has examined whether subacute administration of pycnogenol, a French pine bark extract containing procyanidins that have strong antioxidant potential, alters biomarkers of oxidative stress in normal and diabetic rats. Diabetes was induced in female Sprague-Dawley rats by a single injection of streptozotocin (90 mg/kg body weight, ip), resulting (after 30 days) in subnormal body weight, increased serum glucose concentrations, and an increase in liver weight, liver/body weight ratios, total and glycated hemoglobin, and serum aspartate aminotransferase activity. Normal and diabetic rats were treated with pycnogenol (10 mg/kg body weight/day, ip) for 14 days. Pycnogenol treatment significantly reduced blood glucose concentrations in diabetic rats. Biochemical markers for oxidative stress were assessed in the liver, kidney, and heart. Elevated hepatic catalase activity in diabetic rats was restored to normal levels after pycnogenol treatment. Additionally, diabetic rats treated with pycnogenol had significantly elevated levels of reduced glutathione and glutathione redox enzyme activities. The results demonstrate that pycnogenol alters intracellular antioxidant defense mechanisms in streptozotocin-induced diabetic rats.     

Cadmium-induced oxidative stress and DNA damage in kidney of pregnant female rats

In the present study, we have investigated the influence of sub-acute treatment with cadmium (Cd) on some parameters indicative of oxidative stress and DNA damage in tissues of pregnant female rats. Pregnant female rats (n=6) were injected subcutaneously, daily with a dose of cadmium chloride of 3 mg/kg body weight (b.w.) from day 6 to day 19 of pregnancy, and they were allowed to deliver normally. MDA level and GPx, CAT and SOD activities were used as markers of oxidative stress in liver and kidney. The 8-oxo-dG level was measured by the HPLC-EC system. Cd treatment increased MDA (+116%, p<0.01) in kidney. Moreover, Cd treatment also decreased CuZn-SOD (-11%, p<0.05) and GSH level (-52%, p<0.05) in kidney. Treated rats displayed an increase of the liver metallothionein (MT) level. Induction of MT in liver was probably implicated in the detoxification of Cd. The high level of Cd (3 mg/kg) used in the present study is partially neutralized by MT in liver, whereas the free fraction could be implicated in the oxidative stress and DNA oxidation observed in kidney. Cd treatment failed to alter 8-oxodGuo, indicating the absence of DNA oxidation in liver; by contrast, the same treatment increased the 8-oxodGuo level (+51%, p<0.05) in the kidney of pregnant female rats, indicating an oxidative stress associated with DNA damage only in kidney.     

Impact of chromium on lipoperoxidative processes and subsequent operation of the glutathione cycle in rat renal system.

Oral administration of K2Cr2O7 to male albino rats at an acute dose of 1500 mg/kg body wt/day for 3 days brought about sharp decrease in the activities of glucose-6-phosphate dehydrogenase and glutathione reductase of kidney epithelial cells. The scavenging system of kidney epithelium is also affected as evident by the highly significant fall in the activities of glutathione peroxidase, superoxide dismutase and catalase which ultimately leads to the increase in lipid peroxidation value in kidney cortical homogenate. However, glutathione-s-transferase activity in cytosol and glutathione and total thiol content in cortical homogenate were not altered. Chronic oral administration of K2Cr2O7 (300 mg/kg body wt/day) for 30 days to rats lead to elevation in the activities of glutathione peroxidase, glutathione reductase, glutathione-s-transferase, superoxide dismutase and catalase with no change in glucose-6-phosphate dehydrogenase activity in epithelial cells. This might lead to the increase in glutathione and total thiol status and decrease in lipid peroxidation value in whole homogenate system.