Taurine plays a beneficial role against cadmium-induced oxidative renal dysfunction

The present study has been carried out to investigate the role of taurine (2-aminoethanesulfonic acid), a conditionally essential amino acid, in ameliorating cadmium-induced renal dysfunctions in mice. Cadmium chloride (CdCl₂) has been selected as the source of cadmium. Intraperitoneal administration of CdCl₂ (at a dose of 4 mg/kg body weight for 3 days) caused significant accumulation of cadmium in renal tissues and lessened kidney weight to body weight ratio. Cadmium administration reduced intracellular ferric reducing/antioxidant power (FRAP) of renal tissues. Levels of serum marker enzymes related to renal damage, creatinine and urea nitrogen (UN) have been elevated due to cadmium toxicity. Cadmium exposure diminished the activities of enzymatic antioxidants, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PD) as well as non-enzymatic antioxidant, reduced glutathione (GSH) and total thiols. On the other hand, the levels of oxidized glutathione (GSSG), lipid peroxidation, protein carbonylation, DNA fragmentation, concentration of superoxide radicals and activities of cytochrome P450 enzymes (CYP P450s) have been found to increase due to cadmium intoxication. Treatment with taurine (at a dose of 100 mg/kg body weight for 5 days) before cadmium intoxication prevented the toxin-induced oxidative impairments in renal tissues. The beneficial role of taurine against cadmium-induced renal damage was supported from histological examination of renal segments. Vitamin C, a well-established antioxidant was used as the positive control in the study. Experimental evidence suggests that both taurine and vitamin C provide antioxidant defense against cadmium-induced renal oxidative injury. Combining all, results suggest that taurine protects murine kidneys against cadmium-induced oxidative impairments, probably via its antioxidative property.     

Farnesol attenuates 1,2-dimethylhydrazine induced oxidative stress, inflammation and apoptotic responses in the colon of Wistar rats

Colon cancer is the major health hazard related with high mortality and it is a pathological consequence of persistent oxidative stress and inflammation. Farnesol, an isoprenoid alcohol, has been shown to possess antioxidant, anti-inflammatory and chemopreventive properties. The present study was performed to evaluate the protective efficacy of farnesol against 1,2-dimethylhydrazine (DMH) induced oxidative stress, inflammatory response and apoptotic tissue damage. Farnesol was administered once daily for seven consecutive days at the doses of 50 and 100 mg/kg body weight in corn oil. On day 7, a single injection of DMH was given subcutaneously in the groin at the dose of 40 mg/kg body weight. Protective effects of farnesol were assessed by using caspase-3 activity, tissue lipid peroxidation (LPO) and antioxidant status as end point markers. Further strengthening was evident on histopathological observations used to assess the protective efficacy of farnesol. Prophylactic treatment with farnesol significantly ameliorates DMH induced oxidative damage by diminishing the tissue LPO accompanied by increase in enzymatic viz., superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and quinone reductase (QR) and non-enzymatic viz., reduced glutathione (GSH) antioxidant status. Farnesol supplementation significantly decreased caspase-3 activity in colonic tissue. Histological findings also revealed that pretreatment with farnesol significantly reduced the severity of submucosal edema, regional destruction of the mucosal layer and intense infiltration of the inflammatory cells in mucosal and submucosal layers of the colon. The data of the present study suggest that farnesol effectively suppress DMH induced colonic mucosal damage by ameliorating oxidative stress, inflammatory and apoptotic responses.     

Effects of diallyl sulfide and zinc on testicular steroidogenesis in cadmium-treated male rats

Cadmium (Cd) is one of the environmental pollutants that affect various tissues and organs including testis. Harmful effect of cadmium on testis is known to be germ cell degeneration and impairment of testicular steroidogenesis. In the present study, the effect of diallyl sulfide (DAS), a sulfur-containing volatile compound present in garlic, and zinc (Zn) was investigated on cadmium-induced testicular toxicity in rats. Male adult Wistar rats treated with cadmium (2.5 mg/kg body wt, five times a week for 4 weeks) showed decreased body weight, paired testicular weight, relative testicular weight, serum testosterone, luteinizing hormone, follicle-stimulating hormone, and testicular total antioxidant capacity (TAC) and protein levels. Testicular steroidogenic enzymes, such as 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and marker enzymes, such as sorbitol dehydrogenase (SDH), lactate dehydrogenase (LDH), acid phosphatase (ACP), alkaline phosphatase (ALP), and glucose-6-phosphate dehydrogenase (G6PD), showed a significant decrease in activities whereas that of gamma-glutamyl transferase was significantly increased after cadmium exposure. The results have revealed that concurrent treatment with DAS or zinc restored key steroidogenic enzymes, SDH, LDH, and G6PD and increased testicular weight significantly. DAS restored the TAC level and increased testosterone level and relative testicular weight significantly. Zinc restored testicular protein level and body weight. It can be concluded that cadmium causes testicular toxicity and inhibits androgen production in adult male rats probably by affecting pituitary gonadotrophins and that concurrent administration of DAS or zinc provides protection against cadmium-induced testicular toxicity.     

Tellurium-induced dose-dependent impairment of antioxidant status: differential effects in cerebrum,cerebellum, and brainstem of mice

The effect of various doses of sodium tellurite (0.4, 0.8, and 2.0 mg/kg body weight, orally) on the activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and catalase) and content of glutathione and thiobarbituric acid reactive substances (TBARSs) in the cerebrum, cerebellum, and brainstem of male albino mice was studied after 15 d of treatment. All of the doses of tellurium (0.4, 0.8, and 2.0 mg/kg body weight, orally) have depleted the activity of antioxidant enzymes and the content of glutathione dose dependently in the cerebrum, cerebellum, and brainstem and it was significant with the dose of 2.0 mg/kg. On the other hand, the 2.0-mg/kg dose of tellurium has significantly elevated the content of TBARSs in the cerebrum and cerebellum. The 0.8-mg/kg dose of tellurium has significantly depleted the activities of glutathione peroxidase in the cerebrum and brainstem, glutathione-S-transferase in the cerebrum and cerebellum, catalase in the brainstem, and the content of glutathione in the cerebrum and cerebellum. In contrast, this dose has significantly elevated the content of TBARSs in the cerebrum and cerebellum. However, the depletion in the activity of glutathione reductase with various doses of sodium tellurite was not significant in any brain part of mice. The result suggests that sodium tellurite differentially affects the antioxidant status within various parts of the mice brain.     

Effect of Physalis peruviana L. on Cadmium-Induced Testicular Toxicity in Rats

Cadmium (Cd) stimulates the production of reactive oxygen species and causes tissue damage. We investigated here the protective effect of Physalis peruviana L. (family Solanaceae) against cadmium-induced testes toxicity in rats. Twenty-eight Wistar albino rats were used. They were divided into four groups (n?=?7). Group 1 was used as control. Group 2 was intraperitoneally injected with 6.5 mg/kg body weight (bwt) of cadmium chloride for 5 days. Group 3 was orally treated with 200 mg/kg bwt of methanolic extract of physalis (MEPh). Group 4 was pretreated with MEPh before cadmium for 5 days. Changes in body and testes weights were determined. Oxidative stress markers, antioxidant enzymes, and testosterone level were measured. Histopathological changes of testes were examined, and the immunohistochemical staining for the proapoptotic (caspase-3) protein was performed. The injection of cadmium caused a significant decrease in body weight, while a significant increase in testes weight and testes weight index was observed. Pretreatment with MEPh was associated with significant reduction in the toxic effects of Cd as shown by reduced testicular levels of malondialdehyde, nitric oxide, and caspase-3 expression and increased glutathione content, and the activities of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and testosterone were also increased. Testicular histopathology showed that Cd produced an extensive germ cell apoptosis, and the pretreatment of MEPh in Cd-treated rats significantly reduced Cd-induced testicular damage. On the basis of the above results, it can be hypothesized that P. peruviana L. has a protective effect against cadmium-induced testicular oxidative stress and apoptosis in the rat.     

Involvement of a cadmium-induced low molecular weight protein in regulating cadmium toxicity in the diazotrophic cyanobacterium Anabaena doliolum

This study demonstrated the production of a cadmium-induced low molecular weight (3.5 kDa), buthionine sulfoximine (BSO) sensitive protein in Anabaena doliolum. Production of this protein was accompanied by a decrease in the glutathione level of the cell. Cadmium was found to be differentially toxic to carbon fixation, O₂ evolution, ATP content, nitrate reductase, nitrogenase, alkaline phosphatase and ATPase of control (untreated), BSO, cadmium and (cadmium + BSO) pre-treated A. doliolum. Toxicity was maximum in BSO-grown cells followed be control (untreated), cadmium + BSO and least in cadmium-grown A. doliolum. Cadmium and (cadmium + BSO)-grown cells registered an increased lipid production, reduced metal uptake and low K⁺, Na⁺ loss. In spite of equal cadmium uptake rates, a significant difference in toxicity between cadmium-grown and (cadmium + BSO)-grown cultures was, however, noticed. Better performance of physiological and biochemical variables of cadmium-grown A. doliolum and its tolerance to cadmium could be due to the synthesis of low molecular weight cadmium binding protein (presumably phytochelatin) as well as an increased production of lipid.     

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.     

Induction of necrosis in cadmium-induced hepatic oxidative stress and its prevention by the prophylactic properties of taurine

The present study has been carried out to investigate the protective role of taurine against cadmium (Cd)-induced oxidative impairment in murine liver. Oral administration of cadmium chloride (CdCl₂) at a dose of 4 mg/kg body weight for 6 days increased the accumulation of the Cd in the liver and diminished the liver weight to body weight ratio. The CdCl₂ altered the levels of intracellular trace elements, cofactors of various metalloenzymes and increased the activities of serum marker enzymes related to liver dysfunction. In addition, Cd intoxication also attenuated intracellular antioxidant power, the activities of antioxidant enzymes as well as the levels of cellular metabolites. Moreover, level of hepatic metallothionein, lipid peroxidation, protein carbonylation, DNA fragmentation, concentration of intracellular reactive oxygen species (ROS) and the activities of cytochrome P450s have been increased due to Cd toxicity. In addition to the oxidative impairments, Cd exposure caused hepatic cell death mainly via the necrotic pathway. Oral administration of taurine at a dose of 100 mg/kg body weight for 5 days prior to CdCl₂ intoxication prevented the alterations of all the toxic-induced hepatic damages. Histological studies also supported the beneficial role of taurine against Cd-induced hepatic damages. Combining all, results suggest that taurine could protect hepatic tissues against Cd-induced oxidative stress probably through its antioxidant activity.     

Antiatherogenic effect of taurine in high fat diet fed rats

The role of taurine on atherogenesis induced by high fat diet in rats, a species which depends entirely on taurine for conjugation of bile acids has been investigated. Wistar male rats were fed on (p.o.) taurine in addition to high fat diet (11% coconut oil w/w) for 6 months. High fat diet caused significant increase of serum total cholesterol (2 fold), serum triglycerides (92.6%), LDL cholesterol (92.3%) and body weight gain (2.8 fold). Taurine administration significantly reduced serum cholesterol (37%), triglycerides (94.5%), LDL cholesterol (34%), body weight (46%). It also significantly reduced aortic cholesterol and thiobarbituric acid reactive substances and there was a significant increase of reduced glutathione. Taurine significantly increased fecal bile acids which may have resulted in significant decrease of serum cholesterol. Aortic lesion index was significantly decreased in the taurine administered group suggesting the antiatherogenic effect of taurine. It is concluded that taurine attenuated the atherogenesis possibly by its hypocholesterolemic and antioxidant property.     

Effects of ascorbic acid on cadmium-induced oxidative stress and performance of broilers

The effects of cadmium on performance, antioxidant defense system, liver and kidney functions, and cadmium accumulation in selected tissues of broiler chickens were studied. Whether the possible adverse effects of cadmium would reverse with the antioxidant ascorbic acid was also investigated. Hence, 4 treatment groups (3 replicates of 10 chicks each) were designed in the study: control, ascorbic acid, cadmium, and cadmium plus ascorbic acid. Cadmium was given via the drinking water at a concentration of 25 mg/L for 6 wk. Ascorbic acid was added to the basal diet at 200 mg/kg either alone or with cadmium. Cadmium decreased the body weight (BW), body weight gain (BWG), and feed efficiency (FE) significantly at the end of the experiment, wheras its effect on feed consumption (FC) was not significant. Cadmium increased the plasma malondialdehyde (MDA) level as an indicator of lipid peroxidation and lowered the activity of blood superoxide dismutase (SOD). Liver function enzymes, aspartate amino transferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and gamma glutamyl transferase (GGT) activities were not changed by cadmium. Cadmium ingestion did not alter serum creatinine levels. Although the serum cadmium level was not elevated, cadmium mainly accumulated in the kidneys, liver, pancreas, and muscle. Ascorbic acid supplementation resulted in a reduction of MDA level previously increased by cadmium and a restoration in SOD activity. However, ascorbic acid did not ameliorate the growth inhibitory effect of cadmium nor did it prevent accumulation of cadmium in analyzed tissues. These data indicate that oxidative stress, induced by cadmium, plays a role in decreasing the performance of broilers and that dietary supplementation by ascorbic acid might be useful in reversing the lipid peroxidation induced by cadmium and partly alleviating the adverse effect of cadmium on performance of broilers.     

Ganoderma lucidum polysaccharides supplementation attenuates exercise-induced oxidative stress in skeletal muscle of mice

The present study was designed to determine the effects of Ganoderma lucidum polysaccharides (GL-PS) on exhaustive exercise-induced oxidative stress in skeletal muscle tissues of mice. The mice were divided into four groups (three GL-PS administered groups and the control group). The control group was administered with distilled water and GL-PS administered groups were administered with GL-PS (50, 100 and 200 mg/kg body weight per day). After 28 days, the mice performed an exhaustive swimming exercise, along with the determination of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) activities and malondialdehyde (MDA) levels in the skeletal muscle of mice. The results showed that GL-PS could increase antioxidant enzymes activities and decrease the MDA levels in the skeletal muscle of mice. This study provides strong evidence that GL-PS supplementation possessed protective effects against exhaustive exercise-induced oxidative stress.     

Potential chemoprevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by polyphenolics from Acacia nilotica bark

Chemopreventive potential of Acacia nilotica bark extract (ANBE) against single intraperitoneal injection of N-nitrosodiethylamine (NDEA, 200 mg/kg) followed by weekly subcutaneous injections of carbon tetrachloride (CCl₄, 3 ml/kg) for 6 weeks induced hepatocellular carcinoma (HCC) in rats was studied. At 45 day after administration of NDEA, 100 and 200 mg/kg of ANBE were administered orally once daily for 10 weeks. The levels of liver injury and liver cancer markers such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (γ-GT), total bilirubin level (TBL), α-feto protein (AFP) and carcinoembryonic antigen (CEA) were substantially increased following NDEA treatment. However, ANBE treatment reduced liver injury and restored liver cancer markers. ANBE also significantly prevented hepatic malondialdehyde (MDA) formation and reduced glutathione (GSH) in NDEA-treated rats which was dose dependent. Additionally, ANBE also increased the activities of antioxidant enzymes viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) in the liver of NDEA-administered rats. Eventually, ANBE also significantly improved body weight and prevented increase of relative liver weight due to NDEA treatment. Histological observations of liver tissues too correlated with the biochemical observations. HPLC analysis of ANBE showed the presence of gallic, protocatechuic, caffeic and ellagic acids, and also quercetin in ANBE. The results strongly support that A. nilotica bark prevents lipid peroxidation (LPO) and promote the enzymatic and non-enzymatic antioxidant defense system during NDEA-induced hepatocarcinogenesis which might be due to activities like scavenging of oxy radicals by the phytomolecules in ANBE.     

Modulation of Glutathione and Glutathione Dependent Antioxidant Enzymes in Mouse Heart Following Doxorubicin Therapy

The toxicity of the antineoplastic agent doxorubicin (DOX) has been shown to be moderated by the antioxidant enzyme glutathione peroxidase. It has been reported that acute doses of DOX can cause an inhibition of glutathione peroxidase in cardiac tissue, that may render this tissue especially susceptible to further prooxidant damage. In this study, multiple DOX treatments at a therapeutic dose were assessed for their effect on the antioxidant enzyme status of cardiac and kidney tissue. DOX was administered i.p. (5 mg/kg) once a week for two weeks to male balb/c mice. The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPOX) and glutathione reductase (GR) were measured 1, 2 and 7 days following the second DOX treatment in both heart and kidney. Levels of reduced glutathione (GSH) were also measured in cardiac tissue at these same times. Cardiac levels of GPOX and GR showed a time-dependent decrease in activity, with 10% and 12% inhibition for GPOX and GR, respectively, at 7 days post second treatment. Cardiac levels of GSH also showed a significant decrease, approximately 15%, at 7 days post second treatment. Cardiac levels of SOD and CAT as well as kidney levels of all four antioxidant enzymes were not affected by DOX treatment. These data suggest that DOX given in a therapeutic regimen, at a therapeutic dose, can cause decreases in cardiac levels of GPOX, GR and GSH that could render the heart especially susceptible to further oxidative challenge.     

Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: protection against reactive oxygen and nitrogen species-induced cell injury

Understanding the molecular pathway(s) of antioxidant gene regulation is of crucial importance for developing antioxidant-inducing agents for the intervention of oxidative cardiac disorders. Accordingly, this study was undertaken to determine the role of Nrf2 signaling in the basal expression as well as the chemical inducibility of endogenous antioxidants and phase 2 enzymes in cardiac fibroblasts. The basal expression of a scope of key cellular antioxidants and phase 2 enzymes was significantly lower in cardiac fibroblasts derived from Nrf2-/- mice than those from wild type control. These include catalase, reduced glutathione (GSH), glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NQO1). Incubation of Nrf2+/+ cardiac fibroblasts with 3H-1,2-dithiole-3-thione (D3T) led to a significant induction of superoxide dismutase (SOD), catalase, GSH, GR, glutathione peroxidase (GPx), GST, and NQO1. The inducibility of SOD, catalase, GSH, GR, GST, and NQO1, but not GPx by D3T was completely abolished in Nrf2-/- cells. The Nrf2-/- cardiac fibroblasts were much more sensitive to reactive oxygen and nitrogen species-mediated cytotoxicity. Upregulation of antioxidants and phase 2 enzymes by D3T in Nrf2+/+ cardiac fibroblasts resulted in a dramatically increased resistance to the above species-induced cytotoxicity. In contrast, D3T-treatment of the Nrf2-/- cells only provided a slight cytoprotection. Taken together, this study demonstrates for the first time that Nrf2 is critically involved in the regulation of the basal expression and chemical induction of a number of antioxidants and phase 2 enzymes in cardiac fibroblasts, and is an important factor in controlling cardiac cellular susceptibility to reactive oxygen and nitrogen species-induced cytotoxicity.     

Caffeine decreases the occurrence of cadmium-induced forelimb ectrodactyly in C57BL/6J mice

BACKGROUND: Cadmium is a well-known animal teratogen. Caffeine is an alkaloid widely consumed by humans. Interactions between teratogens and nonteratogenic doses of other agents are becoming widely studied, as they may shed light on understanding mechanisms of teratogenicity or possible prevention of teratogenic effects. METHODS: C57BL/6JBK mice were injected intraperitoneally (ip) with cadmium sulfate (Cd) at 0, 1.00 (LDCd), 2.50 (MDCd), or 5.00 (HDCd) mg/kg, immediately followed by subcutaneous (sc) administration of 0 or 50 mg/kg caffeine (CAFF) on gestation day (GD) 9. Fetuses were examined on GD 18 for ectrodactyly and other gross morphological malformations. RESULTS: Amelioration of cadmium-induced forelimb ectrodactyly by CAFF was seen in both the high-dose cadmium (HDCd = 65.4%, HDCd+CAFF = 39.2%) and medium-dose cadmium (MDCd = 46.2%, MDCd+ CAFF = 20.8%) treatment groups (P < 0.025). Bilateral expression of ectrodactyly was also decreased in the presence of caffeine. A statistically significant reduction in Cd-induced abnormalities, including: eye, abdominal, and other skeletal defects, was not seen with caffeine addition, although they did trend downward in the caffeine-supplemented groups. Litter size, fetal weight, fetal mortality, and dam weight also were not affected by co-treatment with caffeine. CONCLUSIONS: This study provides evidence that a subteratogenic dose of caffeine can ameliorate cadmium-induced forelimb ectrodactyly in the Cd-sensitive C57BL/6J inbred mouse strain.     

Effect of cadmium on lipid peroxidation and activities of antioxidant enzymes in growing pigs

Malondialdehyde (MDA), glutathione (GSH) content, total antioxidant capacity (T-AOC) levels, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione transferase (GST) activities were studied in serum, liver, and kidney of growing pigs after graded doses of cadmium administration in diets. One hundred ninety-two barrows (Duroc x Landrace x Yorkshire), with similar initial body weight 27.67±1.33 kg, were randomly allotted into 4 different treatments with 3 replications (16 pigs per replication). The treatments received the same basal diet added with 0, 0.5, 5.0, and 10.0 mg/kg cadmium (as CdCl₂), respectively. The results showed pigs treated with 10 mg/kg cadmium significantly decreased average daily gain (ADG) (p<0.05) and increased feed/gain ratio (F/G) (p<0.05) compared to the control. In this treatment, the contents of MDA increased significantly (p<0.05), GSH concentrations, T-AOC levels, and the activities of SOD, GSH-PX, and GST decreased significantly (p<0.05). The results indicate 10 mg/kg cadmium could decrease pig antioxidant capacity after extended exposure and cadmium-induced increase lipid peroxidation might not be only the result of the possibility of lower level of GSH but could also be as a result of direct action of cadmium on peroxidation reaction.     

Schisandrin B protects against tert-butylhydroperoxide induced cerebral toxicity by enhancing glutathione antioxidant status in mouse brain

Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from Fructus Schisandrae, has been shown to produce antioxidant effect on rodent liver and heart. A mouse model of tert-butylhydroperoxide (t-BHP) induced cerebral toxicity was adopted for examining the antioxidant potential of Sch B in the brain. Intracerebroventricular injection of t-BHP caused a time-dependent increase in mortality rate in mice. The t-BHP toxicity was associated with an increase in the extent of cerebral lipid peroxidation and an impairment in cerebral glutathione antioxidant status, as evidenced by the abrupt decrease in reduced glutathione (GSH) level and the inhibition of Se-glutathione peroxidase activity at 5 min following t-BHP challenge. Sch B pretreatment (1 or 2 mmol/kg/day × 3) produced a dose-dependent protection against t-BHP induced mortality. The protection was associated with a decrease in the extent of lipid peroxidation and an enhancement in glutathione antioxidant status in brain tissue detectable at 5 min post t-BHP challenge, with the assessed biochemical parameters being returned to normal values at 60 min in Sch B pretreated mice at a dose of 2 mmol/kg. The ensemble of results suggests the antioxidant potential of Sch B pretreatment in protecting against cerebral oxidative stress.     

Modulatory effects of one polysaccharide from Acanthopanax senticosus in alloxan-induced diabetic mice

One water-soluble polysaccharide ASP was purified from Acanthopanax senticosus and its physicochemical properties were confirmed by the combination of chemical and instrumental analysis. ASP administered orally at three doses (100, 200 and 400 mg/kg body weight) could significantly decrease the concentration of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) cholesterol levels except for high density lipoprotein (HDL) cholesterol level and the relative ratio (HDL/TC) in alloxan-induced diabetic mice, compared with the diabetic controls without drug treatment, comparable with that of diabetic mice treated with metformin. Furthermore, ASP could obviously increase the body weight and serum insulin level and reduce the fasting blood glucose (FBG) levels, especially at dose of 200 mg/kg. The data demonstrated ASP at the certain did often exhibit the optimal protective effect in alloxan-induced diabetic mice. It is promising that ASP may serve as a drug candidate or a healthcare food for diabetic therapy or protection.     

Cadmium induced limb defects in mice: strain associated differences in sensitivity.

Cadmium (CdSO4) was given ip on day 9 at 12 or 24 mumol/kg to pregnant CD-1 (non-inbred) mice. Fetuses showed malformations of the limbs, face, trunk, and tail. There was a statistically significant relationship between the dose of cadmium and the malformation rate. Cadmium (12 mumol/kg ip on day 9) was then given to mice of six inbred strains three of which (A/J, BALB/cJ, and C57BL6J) carry a gene cdm for resistance to cadmium-induced testicular damage, and three strains (AKR/J, CBA/J, and DBA/2J) which do not. Paradoxically, the three strains resistant to cadmium induced testicular damage were significantly more sensitive to its teratogenic effects than were the other three strains. In all inbred strains most malformations involved the limbs. All forelimb defects found in inbred or non-inbred cadmium treated mice were postaxial and indistinguishable from those produced by acetazolamide in mice. The remarkable similarity of the cadmium- and acetazolamide-induced forelimb malformations may be a reflection of the limited number of ways that a rodent forelimb can react to a teratogenic insult. The hindlimb defects were all preaxial.     

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.