Diphenyl diselenide protects against glycerol‐induced renal damage in rats

In this study we evaluated the effect of diphenyl diselenide (PhSe)₂ on glycerol‐induced acute renal failure in rats. Rats were pre‐treated by gavage every day with (PhSe)₂ (7.14 mg kg^?1) for 7 days. On the eighth day, rats received an intramuscular injection of glycerol (8 mL kg^?1). Twenty‐four hours afterwards, rats were euthanized and the levels of urea and creatinine were measured in plasma. Catalase (CAT), glutathione peroxidase (GPx), glutathione S‐transferase (GST), δ‐aminolevulinate dehydratase (δ‐ALA‐D) and Na⁺, K⁺‐ATPase activities and ascorbic acid levels were evaluated in renal homogenates. Histopathological evaluations were also performed. The results demonstrated that (PhSe)₂ was able to protect against the increase in urea and creatinine levels and histological alterations in kidney induced by glycerol. (PhSe)₂ protected against the inhibition in δ‐ALA‐D, CAT and GPx activities and the reduction in ascorbic acid levels induced by glycerol in kidneys of rats. In conclusion, the present results indicate that (PhSe)₂ was effective in protecting against acute renal failure induced by glycerol. Copyright © 2009 John Wiley & Sons, Ltd.     

Melatonin protects against mercury(II)-induced oxidative tissue damage in rats

Mercury exerts a variety of toxic effects in the body. Lipid peroxidation, DNA damage and depletion of reduced glutathione by Hg(II) suggest an oxidative stress-like mechanism for Hg(II) toxicity. Melatonin, the main secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. N-Acetylcysteine, a precursor of reduced glutathione and an antioxidant, is used in the therapy of acute heavy metal poisoning. In this study the protective effects of melatonin in comparison to that of N-acetylcysteine against Hg-induced oxidative damage in the kidney, liver, lung and brain tissues were investigated. Wistar albino rats of either sex (200-250 g) were divided into six groups, each consisting of 8 animals. Rats were intraperitoneally injected with 1) 0.9% NaCl, control (C) group; 2) a single dose of 5 mg/kg mercuric chloride (HgCl2), Hg group; 3) melatonin in a dose of 10 mg/kg, 1 hr after HgCl2 injection, Hg-melatonin group; 4) melatonin in a dose of 10 mg/kg one day before and 1 hr after HgCl2 injection, melatonin-Hg-melatonin group; 5) N-acetylcysteine in a dose of 150 mg/kg, 1 hr after HgCl2 injection, Hg-N-acetylcysteine group, and 6) N-acetylcysteine in a dose of 150 mg/kg one day before and 1 hr after HgCl2 injection, N-acetylcysteine-Hg-N-acetylcysteine group. Animals were killed by decapitation 24 hr after the injection of HgCl2. Tissue samples were taken for determination of malondialdehyde, an end-product of lipid peroxidation; glutathione (GSH), a key antioxidant, and myeloperoxidase activity, an index of neutrophil infiltration. The results revealed that HgCl2 induced oxidative tissue damage, as evidenced by increases in malondialdehyde levels. Myeloperoxidase activity was also increased, and GSH levels were decreased in the liver, kidney and the lungs. All of these effects were reversed by melatonin or N-acetylcysteine treatment. Since melatonin or N-acetylcysteine administration reversed these responses, it seems likely that melatonin or N-acetylcysteine can protect all these tissues against HgCl2-induced oxidative damage.     

Quillaja saponaria bark saponin protects Wistar rats against ferrous sulphate-induced oxidative and inflammatory liver damage

Context: Saponins from different sources are historically reported in Chinese medicine to possess many beneficial effects. However, insufficient experimental data are available regarding the hepatoprotective potential of Quillaja bark saponin.

Objective: The protective effect of Quillaja saponaria Molina (Quillajaceae) bark triterpenoid saponin against iron-induced hepatotoxicity is compared to the standard N-acetylcysteine in adult male Wistar rats.

Materials and methods: Animals were divided into (six) groups, namely a normal control, an N-acetylcysteine control (300?mg/kg/day, p.o., 10?days), a saponin control (100?mg/kg/day, p.o., for 10?days), a hepatotoxicity control (two doses of ferrous sulphate, 30?mg/kg/day each, i.p., on 9th and 10th day), an N-acetylcysteine plus ferrous sulphate (standard treatment) and a saponin plus ferrous sulphate (test treatment) group. Hepatocyte integrity loss markers (serum ALT, AST, ALP, GGT and LDH), oxidative stress markers (hepatic MDA, GSH and NO_x), dyslipidaemic markers (serum TC and TG) and hepatocyte functioning markers (serum bilirubin and albumin) were assessed.

Results: Quillaja bark saponin decreased iron-induced elevation of ALT (reaching 57% of hepatotoxicity control), AST (66%), ALP (76%), GGT (60%), LDH (54%), MDA (65%), NO_x (77%), TC (70%), TG (54%), and total (54%), direct (54%) and indirect (54%) bilirubin, coupled with increased GSH (219%) and albumin (159%) levels. Histopathological study strongly supported biochemical estimations, while immunohistochemical study showed marked effect on eNOS and iNOS expression.

Conclusions: Quillaja bark saponin has a good hepatoprotective effect. Amelioration of oxidative stress and suppression of NOS expression, with resultant maintenance of hepatocyte integrity and functioning, may explain this beneficial effect.     

Picroliv protects against monocrotalineinduced hepatic damage in rats

Monocrotaline, a pyrrolizidine alkaloid, caused changes in most of the biochemical parameters in rats 12 days after a single dose of 120 mg/kg. These included significantly increased activities of hepatic succinate dehydrogenase, acid ribonuclease, acid phosphatase, gammaglutamyl transpeptidase and 5'-nucleotidase and decreased in the activities of glucose-6-phosphatase and cytochrome P450. The levels of DNA, RNA and glycogen in liver and albumin and protein in serum decreased while serum bilirubin increased. The histopathological changes in liver were characterized by diffused hepatocyte alterations in the form of ballooning, granular cytoplasm, indistinct cell outlines, nuclear changes, focal necrosis, and vascular damage. When picroliv, a standardized iridoid glycoside fraction of Picrorhiza kurroa, was administered orally in a dose of 25 mg/kg simultaneously with monocrotaline, alterations in most of the biochemical parameters along with the histopathological changes in liver caused by monocrotaline were prevented.     

Endocrine and testicular changes induced by olanzapine in adult Wistar rats

Olanzapine is an atypical antipsychotic drug that has been increasingly used in acute treatment of, and therapeutic support for, schizophrenia, bipolar disorder and other psychoses. Considering that olanzapine acts on the dopaminergic receptor and this receptor is detected in germ cells, the present study aims to investigate the effects of treatment with different doses of olanzapine on spermatogenesis, plasma testosterone and weight of androgen‐dependent organs in rats. Results showed reduced plasma testosterone levels, and reduced testis, epididymis and prostate weights. Histopathologic and histomorphometric analysis of spermatogenesis indicated testicular degeneration. Furthermore, germ cell desquamation, syncytial multinucleated cells, Sertoli cell vacuolization and presence of necrotic and apoptotic germ cells wwew observed. Olanzapine treatment in rats promoted endocrinological changes and lesions in the testis, leading to a disturbance in spermatogenesis. Copyright © 2011 John Wiley & Sons, Ltd.     

Camellia sinensis (green tea) extract attenuate acrylamide induced testicular damage in albino rats

Acrylamide is a proved toxin for testicular function, found in food when heated for long period of time. Green tea (Camellia sinensis) is a potent antioxidant; the aim of this study was to investigate the protective effect of green tea extract against the toxic effects of acrylamide in rat testes. Methods: acrylamide was administered orally to rats in different doses and also the extract of green tea was administered orally to different groups of animals in combination with the acrylamide. The weight of animals, testosterone hormone level and histopathological effect upon testicles were evaluated. Results: Testosterone hormone level in serum, and histopathological findings were significantly improved with the co‐administration of green tea extract with the acrylamide. Green tea extract reversed all the toxic effects of acrylamide even in high dose for long period (90 days). Conclusion: Green tea extract is a potent antioxidant antidote for the acrylamide toxic effects upon testicular function. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1155–1161, 2014.     

beta-glucan protects against burn-induced oxidative organ damage in rats

Thermal injury may lead to systemic inflammatory response, and multiple organ failure. Generation of reactive oxygen radicals and lipid peroxidation play important roles in burn-induced remote organ injury. In the present study, we investigated the putative protective effect of local or systemic beta-glucan treatment on burn-induced remote organ injury. Wistar albino rats were exposed to 90 degrees C bath for 10 s to induce thermal trauma. beta-glucan (3.75 mg/rat locally or 50 mg/kg orally) or saline was administered immediately after the trauma and were repeated twice daily in 48 h groups. Rats were decapitated either 6 or 48 h after burn injury and the skin, lung, liver, ileum and kidney tissues were taken for the measurement of malondialdehyde (MDA)--an index of lipid peroxidation--and glutathione (GSH)--a key antioxidant--levels. Neutrophil infiltration was evaluated by the measurement of tissue myeloperoxidase (MPO) activity, while the tumor necrosis factor-alpha (TNF-alpha) levels were measured in serum samples. Skin tissues were also examined microscopically. Severe skin scald injury (30% of total body surface area) caused significant decreases in GSH levels of the liver and intestinal tissues (p<0.01-<0.001), while MDA levels were significantly (p<0.01-p<0.001) increased at post-burn 6 and 48 h. Both local and systemic beta-glucan treatments significantly reversed (p<0.01-p<0.001) the elevations in MDA levels, while reduced GSH levels were reversed back to control levels (p<0.01-p<0.001); and the raised MPO levels were significantly decreased (p<0.05-p<0.001). The results indicate that both systemic and local administration of beta-glucan were effective against burn-induced oxidative tissue damage in the rat. beta-glucans, besides their immunomodulatory effects, have additional antioxidant properties. Therefore, beta-glucans merit consideration as therapeutic agents in the treatment of burn injuries.     

Mimosa (Mimosa caesalpiniifolia) prevents oxidative DNA damage induced by cadmium exposure in Wistar rats

The Mimosa (Mimosa caesalpiniifolia) is a plant native from South America; it is used in the traditional medicine systems for treating bacterial, fungal, parasitic and inflammatory conditions. The aim of this study was to evaluate the antigenotoxic and antioxidant activities induced by mimosa (M. caesalpiniifolia) in multiple rodent organs subjected to intoxication with cadmium chloride. A total of 40 Wistar rats (8?weeks old, 250?g) were distributed into eight groups (n?=?5), as follows: Control group (non-treated group, CTRL); Cadmium exposed group (Cd); cadmium exposure and treated with extract at 62.5?mg/kg/day; cadmium exposure and treated with extract at 125?mg/kg/day; cadmium exposure and treated with extract at 250?mg/kg/day; cadmium exposure and treated with ethyl acetate fraction at 62.5?mg/kg/day. For evaluating the toxicogenetic potential of mimosa, two groups were included in the study being treated with extract at 250?mg/kg/day and acetate fraction of mimosa at 62?mg/kg/day, only. Extract of mimosa at concentrations of 62.5 and 125?mg decreased DNA damage in animals intoxicated with cadmium when compared to cadmium group. In a similar manner, treatment with ethyl acetate fraction of mimosa at 62.5?mg concentration in animals previously exposed to cadmium reduced genetic damage in peripheral blood cells. In a similar manner, the treatment with ethyl acetate fraction reduced DNA damage in liver cells. Oxidative DNA damage was reduced to animals exposed to cadmium and treated with 125?mg of extract as well as those intoxicated to cadmium and treated with 62.5 of acetate fraction of mimosa. Taken together, our results indicate that mimosa prevents genotoxicity induced by cadmium exposure in liver and peripheral blood cells of rats as a result of antioxidant activity.     

Insights into testicular damage induced by ethinylestradiol in rats

The present study was conducted to clarify the mechanisms of testicular toxicity induced by ethinylestradiol using a rat model maintaining testicular testosterone levels. Twelve-week-old male SD rats were implanted subcutaneously with testosterone (800 mg)-filled tubes on the back 2 days before ethinylestradiol treatment, and subsequently administered orally 10 mg/kg/day ethinylestradiol for 4 consecutive weeks. At termination, measurements of hormone levels in serum and the testis, sperm head counts in the testis, weights of genital organs and histopathological examination were performed. Results show that the supply of testosterone alone induced markedly increased serum testosterone levels, slightly decreased testicular testosterone levels, and atrophic Leydig cells. Treatment of rats with ethinylestradiol alone significantly decreased testosterone levels in serum and the testis, sperm head counts, and weights in the testis, epididymis and prostate. Histological features included atrophy of Leydig cells, decreased number of elongated spermatids, degeneration of germ cells, and tubular atrophy. Co-administration of testosterone almost completely prevented the aforementioned changes brought about by ethinylestradiol, except for Leydig cell atrophy. From these results, we attribute testicular toxicity during ethinylestradiol exposure to the suppression of testicular testosterone levels.     

Influence of combined antioxidants against cadmium induced testicular damage

Acute effects of cadmium (Cd) and combined antioxidants were evaluated in Sprague–Dawley rat testes. The rats were subdivided into four groups. Cadmium chloride (2 mg/kg day) injected intraperitoneally during 8 days. Vitamin C (250 mg/kg day), vitamin E (250 mg/kg day) and sodium selenate (0.25 mg/kg day) were pretreated by gavage in both of control and cadmium injected rats. Testis lipid peroxidation and glutathione levels were determined by spectrophotometrically. In Cd treated rats, lipid peroxidation levels were increased and glutathione levels were decreased and combined antioxidants treatment was effective in preventing of lipid peroxidation and normalizing glutathione. In Cd treated animals, the degenerative changes were observed, but not observed in the administrated rats with Cd and antioxidants under the light microscope. Proliferating cell nuclear antigen, metallothionein and caspase-3 activities were evaluated by immunohistochemically. Proliferation activity was not seen in the spermatogonial cells of cadmium treated testis. Treatment with antioxidants in cadmium administrated testis leads to pronounced increase in proliferation activity. Cytoplasmic caspase-3 activity was determined in the spermatogenic cells but not spermatogonia in treatment of antioxidants with Cd. In control and treated with antioxidants animals, metallothionein expressions were localized in the cells of seminiferous tubules, although the expression only was observed in the interstitial cells of cadmium treated rats. Results demonstrated beneficial effects of combined vitamin C, vitamin E and selenium treatment in Cd toxicity.     

Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats

Oxidative stress plays a pivotal role in the pathogenesis and progression of gamma-irradiation induced cellular damage and the administration of dietary antioxidants has been suggested to protect against the subsequent tissue damage. Here, we present the data to explore the hepatoprotective and antioxidant effect of hesperidin, a naturally occurring citrus flavanoglycone, against gamma-irradiation induced oxidative damage in the liver of rats. Healthy male Sprague-Dawley rats were exposed to gamma-irradiation (1 Gy, 3 Gy and 5 Gy) and were administered hesperidin (50 mg/kg and 100 mg/kg, b.w, orally) for 7 days post irradiation. The changes in body weight, liver weight, spleen index, serum and liver aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and serum ceruloplasmin levels were determined along with differences in the liver histopathology. Liver thiobarbuturic acid reactive substance as an index for lipid peroxidation and the levels of enzymatic antioxidants like superoxide dismutase, catalase, glutathione peroxidase and the status of non-enzymatic antioxidants as an index for oxidative stress were also determined. Exposure to gamma-irradiation resulted in hepatocellular damage in a dose-dependent manner, featuring a significantly decreased body weight and liver weight and higher levels of serum AST, ALT, ALP, LDH and gamma-GT levels and a simultaneous decrease in their levels in the liver tissue. Oxidative stress was evidenced by elevated levels of lipid peroxidation and a decrease in the levels of key enzymatic and non-enzymatic antioxidants in the liver. However, the gamma-irradiation induced toxic effects were dramatically and dose-dependently inhibited by hesperidin treatment as observed by the restoration in the altered levels of the marker enzymes, lipid peroxidation, enzymatic and non-enzymatic antioxidants. The results of the biochemical observations were supported by the histopathological findings. Thus, oral administration of hesperidin was found to offer protection against gamma-irradiation induced hepatocellular damage and oxidative stress in rats, probably by exerting a protective effect against hepatocellular necrosis via its free radical scavenging and membrane stabilizing ability.     

Protective effect of hemin against cadmium-induced testicular damage in rats

The protective effect of hemin, the heme oxygenase-1 inducer, was investigated in rats with cadmium induced-testicular injury, in which oxidative stress and inflammation play a major role. Testicular damage was induced by a single i.p. injection of cadmium chloride (2 mg/kg). Hemin was given for three consecutive days (40 μmol/kg/day, s.c.), starting 1 day before cadmium administration. Hemin treatment significantly increased serum testosterone level that was reduced by cadmium. Hemin compensated deficits in the antioxidant defense mechanisms (reduced glutathione, and catalase and superoxide dismutase activities), and suppressed lipid peroxidation in testicular tissue resulted from cadmium administration. Also, hemin attenuated the cadmium-induced elevations in testicular tumor necrosis factor-α and nitric oxide levels, and caspase-3 activity. Additionally, hemin ameliorated cadmium-induced testicular tissue damage observed by light and electron microscopic examinations. The protective effect afforded by hemin was abolished by prior administration of zinc protoporphyrin-IX, the heme oxygenase-1 inhibitor. It was concluded that hemin, through its antioxidant, anti-inflammatory and antiapoptotic effects, represents a potential therapeutic option to protect the testicular tissue from the detrimental effects of cadmium.     

Ginkgo biloba extract protects against mercury(II)-induced oxidative tissue damage in rats.

Mercury(II) is a highly toxic metal which induces oxidative stress in the body. In this study we aimed to investigate the possible protective effect of Ginkgo biloba (EGb), an antioxidant agent, against experimental mercury toxicity in rat model. Following a single dose of 5mg/kg mercuric chloride (HgCl(2); Hg group) either saline or EGb (150mg/kg) was administered for 5days. After decapitation of the rats trunk blood was obtained and the tissue samples from the brain, lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Formation of reactive oxygen species in the tissue samples was monitored by chemiluminescence (CL) technique. BUN, creatinin, ALT, and AST levels and tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) activity were assayed in serum samples. The results revealed that HgCl(2) induced oxidative damage caused significant decrease in GSH level, significant increase in MDA level, MPO activity and collagen content of the tissues. Treatment of rats with EGb significantly increased the GSH level and decreased the MDA level, MPO activity, and collagen contents. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the Hg group as compared to control group. On the other hand, EGb treatment reversed all these biochemical indices. Our results implicate that mercury-induced oxidative damage in brain, lung, liver, and kidney tissues protected by G. biloba extract, with its antioxidant effects.     

Curcumin pretreatment protects against acute acrylonitrile-induced oxidative damage in rats

Acrylonitrile (AN) is widely used in the manufacturing of fibers, plastics and pharmaceuticals. Free radical-mediated lipid peroxidation is implicated in the toxicity of AN. The present study was designed to examine the ability of curcumin, a natural polyphenolic compound, to attenuate acute AN-induced lipid peroxidation in the brain and liver of rats. Male Sprague–Dawley rats were orally administered curcumin at doses of 0 (olive oil control), 50 or 100 mg/kg bodyweight daily for 7 consecutive days. Two hours after the last dose of curcumin, rats received an intraperitoneal injection of 50 mg AN/kg bodyweight. Acute exposure to AN significantly increased the generation of lipid peroxidation products, reflected by high levels of malondialdehyde (MDA) both in the brain and liver. These increases were accompanied by a significant decrease in reduced glutathione (GSH) content and a significant reduction in catalase (CAT) activity in the same tissues. No consistent changes in superoxide dismutase (SOD) activity were observed between the control and AN-treatment groups in both tissues. Pretreatment with curcumin reversed the AN-induced effects, reducing the levels of MDA and enhancing CAT activity and increasing reduced GSH content both in the brain and liver. Furthermore, curcumin effectively prevented AN-induced decrease in cytochrome c oxidase activity in both liver and brain. These results establish that curcumin pretreatment has a beneficial role in mitigating AN-induced oxidative stress both in the brains and livers of exposed rats and these effects are mediated independently of cytochrome P450 2E1 inhibition. Accordingly, curcumin should be considered as a potential safe and effective approach in attenuating the adverse effects produced by AN-related toxicants.     

L-ascorbic acid ameliorates postnatal endosulfan induced testicular damage in rats

The aim of the present study is to investigate the effect of L-ascorbic acid on postnatal exposure of endosulfan induced testis damage in the rat. Four groups of seven day old male Wistar rats were treated with 3, 6, 9 and 12 mg/kg endosulfan orally (10 pups/group), from postnatal day 7 to 60 at intervals of 24 h. For 2 more groups (n = 10/group), endosulfan (9 mg/kg and 12 mg/kg) was administered along with L-ascorbic acid (20 mg/kg). The sperm morphology, sperm count and sperm motility was analyzed in all the groups on postnatal day 70. Endosulfan significantly affected the testicular function enhancing the incidence of abnormal spermatozoa, decreasing the sperm count and sperm motility in a dose dependent manner. Abnormalities were of both head and tail and increase in their frequency was more than two-fold of the control value. Sperm count abruptly decreased in 12 mg/kg group and sperm motility decreased up to 50% of the control value. L-ascorbic acid has nullified the toxic effects of the pesticide significantly, but not to the control level. Endosulfan induces the testicular damage following postnatal exposure and L-ascorbic acid prevents the adverse effects considerably in the rat.     

(-)Epigallocatechingallate protects the mitochondria against the deleterious effects of lipids, calcium and adenosine triphosphate in isoproterenol induced myocardial infarcted male Wistar rats

The present study was undertaken to evaluate the protective effect of (-)epigallocatechin gallate (EGCG) on mitochondrial lipids, lipid peroxides, Na(+)/K(+) ATPase, calcium and adenosine triphosphate in isoproterenol (ISO) induced myocardial infarction in male Wistar rats. Rats were pretreated with EGCG (30 mg kg(-1) body weight) orally using an intragastric tube daily for a period of 21 days. After that, ISO (100 mg kg(-1) body weight) was subcutaneously injected to rats at intervals of 24 h for two days. ISO induced rats showed significant increase in the levels of cholesterol, triglycerides and free fatty acids with subsequent decrease in the levels of phospholipids in mitochondrial fraction of the heart. ISO induction also caused significant increase in lipid peroxidation products (thiobarbituric acid reactive substances and lipid hydroperoxides) and significant decrease in the activity of Na(+)/K(+) ATPase in mitochondrial fraction of the heart. A significant increase in the levels of calcium and significant decrease in the levels of adenosine triphosphate were observed in ISO-induced mitochondrial heart. Prior treatment with EGCG (30 mg kg(-1)) significantly protected these alterations and maintained normal mitochondrial function. Thus, this study confirmed the protective effect of EGCG on mitochondria in experimentally induced cardiotoxicity in Wistar rats.     

Vitamin B12 protects against DNA damage induced by hydrochlorothiazide

DNA damage induced by hydrochlorothiazide was previously reported in cultured human lymphocytes. In this study, we aimed to investigate the harmful effects of hydrochlorothiazide on DNA by measuring the spontaneous frequency of sister chromatid exchanges (SCEs) in cultured human lymphocytes. We also aimed to investigate the possible protection of that damage by vitamin B12. The results showed that hydrochlorothiazide (5?µg/mL) significantly increased the frequency of sister chromatid exchanges (P?<?0.001) in human lymphocytes in comparison with control. Additionally, the frequency of hydrochlorothiazide-induced SCEs was significantly decreased by co-treatment with vitamin B12 at concentration of 13.5?µg/mL (P?<?0.001). In conclusion, hydrochlorothiazide is genotoxic to human lymphocytes and its toxicity is reduced by vitamin B12.     

In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats

1. This study examines the activity of the antioxidant N-acetylcysteine on bleomycin-induced pulmonary fibrosis in rats with emphasis on the early inflammatory phase. 2. Rats receiving N-acetylcysteine (300 mg kg(-1) day(-1), intraperitoneal) had less augmented lung wet weight, and lower levels of proteins, lactate dehydrogenase, neutrophil and macrophage counts in bronchoalveolar lavage fluid and lung myeloperoxidase activity with a betterment of histological score at 3 days postbleomycin. 3. A diminished lung GSH/GSSG ratio and augmented lipid hydroperoxides were observed 3 days postbleomycin. These changes were attenuated by N-acetylcysteine. Alveolar macrophages from bleomycin-exposed rats released augmented amounts of superoxide anion and nitric oxide. N-Acetylcysteine did not modify superoxide anion generation but reduced the increased production of nitric oxide. 4. N-Acetylcysteine suppressed the bleomycin-induced increased activation of lung NF-kappaB (shift assay and immunohistochemistry), and decreased the augmented levels of the early inflammatory cytokines, tumour necrosis factor-alpha, interleukin-beta, interleukin-6 and macrophage inflammatory protein-2 observed in bronchoalveolar lavage fluid at 1 and 3 days postbleomycin exposure. 5. At 15 days postbleomycin, N-acetylcysteine decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content: 6351+/-669 and 4626+/-288 micro g per lung in drug vehicle- and N-acetylcysteine-treated rats, respectively; P<0.05). Semiquantitative histological assessment at this stage showed less collagen deposition in N-acetylcysteine-treated rats compared to those receiving bleomycin alone. 6. These results indicate that N-acetylcysteine reduces the primary inflammatory events, thus preventing cellular damage and the subsequent development of pulmonary fibrosis in the bleomycin rat model.     

Renal damage induced by the pesticide methyl parathion in male Wistar rats

Little information is apparently available regarding the nephrotoxic effects induced by pesticides. The aim of this study was to examine the influence of low doses of methyl parathion (MP) on the structure and function of the kidney of male Wistar rats. A corn oil (vehicle) was administered to control rats, whereas treated rats received MP at 0.56 mg/kg orally (1/25 of LD₅₀), every third day, for 8 weeks. At the end of each week following MP exposure, creatinine and glucose levels were measured in plasma, while glucose, inorganic phosphate, total proteins, albumin, and activity of γ-glutamyltranspeptidase (GGT) were determined in urine. Kidney histological study was also performed. Compared with control rats, MP significantly increased plasma glucose and creatinine levels accompanied by decreased urinary flow rate and elevated urinary excretion rates of glucose, phosphate, and albumin. Further, the activity of GGT in urine was increased significantly. The proximal cells exhibited cytoplasmic vacuolization, positive periodic acid Schiff inclusions, and brush border edge loss after 2 or 4 weeks following MP treatment. Finally, renal cortex samples were obtained at 2, 4, 6, and 8 weeks of MP treatment, and the concentrations of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity were measured. The mRNA expression levels of BAX and tumor necrosis factor-α (TNF-α) were also determined (RT-PCR). MP significantly decreased renal GSH levels, increased GPx activity, as well as downregulated the mRNA expression of TNF-α and BAX. Densitometry analysis showed a significant reduction in TNF-α and BAX mRNA expression levels at 2 and 4 weeks following MP treatment. Low doses of MP produced structural and functional damage to the proximal tubules of male rat kidney.