Activation of mitochondria-mediated apoptotic pathway in tri-ortho-cresyl phosphate-induced delayed neuropathy

Previous studies suggest that abnormal neurons death has been implicated in organophosphate-induced delayed neuropathy (OPIDN). However, the precise mechanism of neuronal death in OPIDN remains largely unknown. In this study, adult hens were treated with a dosage of 750 mg/kg tri-ortho-cresyl phosphate (TOCP) by gavage, and then sacrificed on the time-points of 1, 5, 10, and 21 days after dosing TOCP, respectively. The apoptotic change of spinal cord neurons induced by TOCP was examined, and the role of mitochondria-mediated apoptosis of neurons during OPIDN was investigated. TUNEL assays showed that apoptotic neurons in hen spinal cords began to appear on day 5 following TOCP exposure. Immunohistochemistry and western blot analysis revealed a translocation of cytochrome C from mitochondria to cytoplasm after dosing TOCP. Moreover, the level of Bcl-2, Bcl-xl, Pro-caspase3 and Pro-caspase9 in hen spinal cord was significantly decreased, whereas that of Bax and cleaved-PARP was significantly elevated. Taken together, these findings indicate that the administration of TOCP can induce neuron apoptosis in hen spinal cords, which might be mediated by the activation of mitochondrial apoptotic pathway.     

Astragaloside IV ameliorates fat metabolism in the liver of ageing mice through targeting mitochondrial activity

Astragaloside IV (AST) is a major bioactive compound of Radix Astragali with medical and health benefits. Previous studies have found that AST can reduce the body weights of high-fat diet fed mice. However, the effect of AST on fat metabolism of ageing mice is unclear. In this study, naturally ageing mice were administered intragastrically with AST at 30 mg/kg/day (ageing + AST-L group) and 90 mg/kg/day (ageing + AST-H group) for 16–20 months. Adult (4 months old) and ageing mice were given 1% sodium carboxyl methylcellulose as vehicle. Energy metabolism-related biological parameters of living mice were examined. Moreover, mRNA and protein levels of key enzymes/proteins involved in triglyceride (TG) lipolysis, fatty acid β-oxidation (FAO), ketone body (KB) production and mitochondrial respiratory chain were also examined after sacrifice. Results demonstrated that treatment with AST significantly reduced body weight, white fat and liver/body weight ratio of ageing mice, significantly reduced serum/hepatic TG levels, respiratory quotient, promoted fatty acid mobilization in white adipose tissue, mitochondrial FAO and KB production and mitochondrial biosynthesis/functions in the liver of ageing mice. AST also up-regulated the expression of phosphorylated AMP-activated protein kinase, acetyl-CoA carboxylase, acetyl-coenzyme A synthetase, carnitine palmitoyltransferase 1a/1b, enoyl coenzyme A hydratase-short chain, acyl-CoA dehydrogenase medium chain and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase-2 involved in fat metabolism. These results indicated that mitochondrial activity could be the target of AST to treat abnormal fat metabolism during ageing.     

Quercetin supplementation is effective in improving mitochondrial dysfunctions induced by 3-nitropropionic acid: Implications in Huntington's disease

The study was designed to investigate the beneficial effect of quercetin supplementation in 3-nitropropionic acid (3-NP) induced model of Huntington's disease (HD). HD was induced in rats by administering sub-chronic dose of 3-NP, intraperitoneally, twice daily for 17 days. Quercetin was supplemented at a dose of 25 mg/kg body weight by oral gavage for 21 days. At the end of treatment, mitochondrial bioenergetics, mitochondrial swelling, oxidative stress, neurobehavioral deficits and histopathological changes were analyzed. Quercetin supplementation was able to reverse 3-NP induced inhibition of respiratory chain complexes, restore ATP levels, attenuate mitochondrial oxidative stress in terms of lipid peroxidation and prevent mitochondrial swelling. Quercetin administration also restored the activities of superoxide dismutase and catalase along with thiol content in 3-NP treated animals. Beneficial effect of quercetin administration was observed on 3-NP induced motor deficits analyzed by narrow beam walk and footprint analysis. Histopathological analysis of 3-NP treated rats revealed pyknotic nuclei and astrogliosis in striatum, which were reduced or absent in quercetin supplemented animals. Altogether, our results show that quercetin supplementation to 3-NP induced HD animals ameliorated mitochondrial dysfunctions, oxidative stress and neurobehavioral deficits in rats showing potential of this flavonoid in maintaining mitochondrial functions, suggesting a putative role of quercetin in HD management.     

Protection of Selenium on Hepatic Mitochondrial Respiratory Control Ratio and Respiratory Chain Complex Activities in Ducklings Intoxicated with Aflatoxin B<Subscript>1</Subscript>

To investigate the protection of selenium on hepatic mitochondrial functions, 90 7-day-old ducklings were randomly divided into three groups (groups I–III). Group I was used as a blank control. Group II was administered with aflatoxin B₁ (0.1 mg/kg body weight). Group III was administered with aflatoxin B₁ (0.1 mg/kg body weight) plus selenium (sodium selenite, 1 mg/kg body weight). All treatments were given once daily for 21 days. The results showed that the activities of hepatic mitochondrial complexes I–IV in group II ducklings significantly decreased when compared with group I (P < 0.01). Furthermore, the activities of hepatic mitochondrial complexes I–IV in group III significantly increased when compared with group II (P < 0.05). The hepatic mitochondrial respiratory control ratio (RCR) in group II ducklings significantly decreased when compared with group I (P < 0.01). In addition, the hepatic mitochondrial RCR in group III significantly increased when compared with group II (P < 0.05). These results revealed that the aflatoxin B₁ significantly induced hepatic mitochondrial dysfunction in the activities of hepatic mitochondrial respiratory chain complexes I–IV and the RCR in ducklings. However, sodium selenite could significantly ameliorate the negative effect induced by aflatoxin B₁.     

Influence of Selenium on Hepatic Mitochondrial Antioxidant Capacity in Ducklings Intoxicated with Aflatoxin B<Subscript>1</Subscript>

The aim of the study was to investigate the effect of selenium on hepatic mitochondrial antioxidant capacity in ducklings administrated with aflatoxin B₁ (AFB₁). Ninety 7-day-old ducklings were randomly divided into three groups (groups I–III). Group I was used as a blank control. Group II was administered with AFB₁ (0.1 mg/kg body weight). Group III was administered with AFB₁ (0.1 mg/kg body weight) plus selenium (sodium selenite, 1 mg/kg body weight). All treatments were given once daily for 21 days. The results showed that the activities of mitochondrial superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) in group II ducklings significantly decreased when compared with group I (P < 0.01). Furthermore, the content of hepatic mitochondrial malondialdehyde (MDA) significantly increased (P < 0.01). However, the activities of hepatic mitochondrial SOD, CAT, GSH-Px, and GR in group III ducklings significantly increased when compared with group II (P < 0.05). In addition, the content of hepatic mitochondrial MDA significantly decreased (P < 0.01). These results revealed that AFB₁ significantly induced hepatic mitochondrial antioxidant dysfunction. However, sodium selenite could significantly ameliorate the negative effect induced by AFB₁.     

Effect of sakuranin on carbohydrate-metabolizing enzyme activity modifications in streptozotocin-nicotinamide-induced diabetic wistar rats

This study is to assess the glucose lowering activity of sakuranin in diabetes induced rats by streptozotocin (STZ) and nicotinamide (NA). Diabetic rats were treated sakuranin for 45 days (20, 40, 80 mg/kg) by orally. Sakuranin (80 mg/kg body weight) was normalized the changes of abnormal blood glucose plasma glucose and plasma insulin levels. Hence, we have continued the further research with this active dose of 80 mg/kg sakuranin. The plasma glucose and glycosylated hemoglobin (HbA₁c) reduced and insulin, glycogen and hemoglobin levels increased by Sakuranin administration in diabetic rats. Additionally, hexokinase and glucose-6-phophate dehydrogenase activities increased and glucose-6-phosphatase and fructose-1,6-bisphosphatase activities decreased in diabetic condition while administration of treated compound. In this observed result signified that sakuranin may have potential role of diabetic condition rats by evidenced with reducing glucose and increasing insulin and also protect the carbohydrate metabolic changes.     

Forskolin ameliorates mancozeb‐induced testicular and epididymal toxicity in Wistar rats by reducing oxidative toxicity and by stimulating steroidogenesis

In the present study, we have tested the beneficial effects of forskolin in protecting the mancozeb‐induced reproductive toxicity in rats. Adult male Wistar rats were exposed to either mancozeb (500 mg/kg body weight/day) or forskolin (5 mg/kg body weight/day) or both for 65 days and analyzed for spermatogenesis and steroidogenesis and testicular and epididymal oxidative toxicity. A significant decrease in daily sperm production, epididymal sperm count, motile, viable, and hypo‐osmotic swelling‐tail swelled sperm was observed in mancozeb‐treated rats. The activity levels of testicular 3β‐hydroxysteroid dehydrogenase and 17β‐hydroxysteroid dehydrogenase and circulatory testosterone levels were significantly decreased in mancozeb‐treated rats. Exposure to mancozeb resulted in a significant decrease in glutathione levels and superoxide dismutase and catalase activity levels with an increase in lipid peroxidation levels in the testes and epididymis. Coadministration of forskolin mitigated the mancozeb‐induced oxidative toxicity and suppressed steroidogenesis and spermatogenesis.     

Protective effect of aspartate and glutamate on cardiac mitochondrial function during myocardial infarction in experimental rats

The present study investigates the effect of aspartate and glutamate on mitochondrial function during myocardial infarction (MI) in wistar rats. Male albino wistar rats were pretreated with aspartate [100 mg(kgbody weight)(-1) day(-1)] or glutamate [100 mg(kg body weight)(-1) day(-1)] intraperitoneally for a period of 7 days. Following amino acid treatment, MI was induced in rats by subcutaneous injection of isoproterenol [200 mg(kg body weight)(-1) day(-1)] for 2 days at an interval of 24 h. Isoproterenol (ISO) induction resulting in significant (P<0.05) increase in the levels of cardiac mitochondrial lipid peroxidation with a decrease in reduced glutathione level. The activities of glutathione peroxidase and glutathione reductase were significantly (P<0.05) decreased by ISO. ISO-induction also caused significant (P<0.05) decrease in the activities of mitochondrial tricarboxylic acid cycle enzymes (malate dehydrogenase, isocitrate dehydrogenase, succinate dehydrogenase, alpha-ketoglutarate dehydrogenase) and respiratory chain enzymes (NADH dehydrogenase and cytochrome-c-oxidase). ISO significantly (P<0.05) reduced the cytochrome contents, ATP production, ADP/O ratio and oxidation of succinate in state 3/state 4 whereas significantly (P<0.05) increased NADH oxidation. Pretreatment with aspartate or glutamate significantly (P<0.05) reduced the alterations induced by ISO and maintained normal mitochondrial function. The present findings reveal the protective effect of aspartate and glutamate on cardiac mitochondrial function in myocardial infarction-induced rats.     

Doxorubicin induced neuro- and cardiotoxicities in experimental rats: Protection against oxidative damage by Theobroma cacao Stem bark

80 rats, randomly selected, were divided into 3 treatment groups: pre-, co- and post-treatment; consisting of 6 sub-groups each (5 rats per sub-group): baseline, normal saline (2 mL), α-lipoic acid (20 mg/kg body weight), 200 mg/kg, 400 mg/kg or 800 mg/kg body weight Theobroma cacao stem bark aqueous extract (TCAE). All rats except for baseline group were intoxicated with 20 mg/kg body weight doxorubicin (DOX) intraperitoneally. The animals in pre- or post-treatment group received a single dose of DOX (20 mg/kg body weight) intraperitoneally 24 h before or after 7 days’ oral administration with TCAE respectively while those in co-treatment group were co-administered 2.86 mg/kg body weight of DOX with either normal saline, α- lipoic acid or TCAE orally for 7 days. Animals were sacrificed (pre- and post- treatment groups were sacrificed on the ninth day while the co-treatment group sacrificed on the 8th day). Brain and heart tissue samples were harvested for enzyme markers of toxicity, oxidative stress and histopathological examinations. DOX intoxication caused significant decrease in activities of LDH and ACP, and increase in γGT and ALP activities in brain tissues while causing a significant increase in LDH, ACP, γGT activities and decrease in ALP activity in the cardiac tissues. DOX intoxication caused a significant increase in concentrations of H₂O₂ generated, MDA and PC, XO, MPx and NOX activities with concomitant decrease in CAT, SOD, GPx and GST activities, and in concentrations of GSH, AsA and α-Toc in brain and cardiac tissues. Pre-, co- and post-treatment with TCAE at either 200 mg/kg, 400 mg/kg or 800 mg/kg body weight significantly reversed the oxidative damage to the organs induced by DOX-intoxication. The result affirmed that T. cacao stem bark aqueous extract protected against DOX induced oxidative damage in brain and cardiac tissues of experimental rats.     

Adriamycin induced myocardial failure in rats: Protective role of Centella asiatica

Generation of reactive oxygen species and mitochondrial dysfunction has been implicated in adriamycin induced cardiotoxicity. Mitochondrial dysfunction is characterized by the accumulation of oxidized lipids, proteins and DNA, leading to disorganization of mitochondrial structure and systolic failure. The present study was aimed to evaluate the efficacy of Centella asiatica on the mitochondrial enzymes; mitochondrial antioxidant status in adriamycin induced myocardial injury. Adriamycin (2.5 mg/kg body wt., i.p.) induced mitochondrial damage in rats was assessed in terms of decreased activities (p< 0.05) of cardiac marker enzymes (lactate dehydrogenase, creatine phosphokinase, amino transferases), TCA cycle enzymes (isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase, respiratory marker enzymes (NADH-dehydrogenase, cytochrome-C-oxidase), mitochondrial antioxidant enzymes (GPx, GSH, SOD,CAT) and increased (p< 0.05) level of lipid peroxidation. Mitochondrial damage was confirmed by transmission electron microscopic examination. Pre-co-treatment with aqueous extract of Centella asiatica (200 mg/kg body wt, oral) effectively counteracted the alterations in mitochondrial enzymes and mitochondrial defense system. In addition, transmission electron microscopy study confirms the restoration of cellular normalcy and accredits the cytoprotective role of Centella asiatica against adriamycin induced myocardial injury. Our results demonstrated elevated oxidative stress and mitochondrial dysfunction in adriamycin treated rats. Moreover, on the basis of our findings it may be concluded that the aqueous extract of C. asiatica not only possesses antioxidant properties but it may also reduce the extent of mitochondrial damage     

Hepatotoxic effects of acetaminophen. Protective properties of tryptophan derivatives

Rat intoxication with acetaminophen (APAP) (500–1500 mg/kg body weight, intragastrically) caused a considerable dose-dependent decrease in reduced glutathione (GSH) level in both liver cell cytoplasm and mitochondria (at the dose 1500 mg/kg body weight by 60% and 33%, respectively). The decrease in cytoplasmic GSH level was more pronounced than in mitochondria. Despite of significant mitochondrial GSH depletion we did not observe any inactivation of the mitochondrial enzymes: succinate dehydrogenase, α-ketoglutarate dehydrogenase, glutathione peroxidase, and also any decrease in the respiratory activity of liver mitochondria isolated from APAP-intoxicated rats. We have investigated hepatoprotector properties of tryptophan derivatives, melatonin and N-acetyl-nitrosotryptophan (a nitric oxide donor). The pineal gland hormone, melatonin, a known antioxidant (10 mg/kg body weight), did not prevent intramitochondrial GSH, but decreased the APAP hepatotoxicity evaluated as the decrease in the activity of marker enzymes of hepatic damage, ALT and AST and total bilirubin content in blood plasma of intoxicated rats, whereas NNT did not exhibit any hepatoprotective effects.     

Chronic effects of platinum(IV) complex and its diamine ligand on rat heart function: comparison with cisplatin

Mitochondrial dysfunction plays crucial role in the pathologenesis of myocardial infarction (MI). The present study evaluated the protective effect of α-bisabolol against isoproterenol (ISO)-induced mitochondrial dysfunction and apoptosis in rats. Male albino Wistar rats were pre- and co-treated with intraperitoneal injection of α-bisabolol (25 mg/kg body weight) daily for 10 days. To induce experimental MI, ISO (85 mg/kg body weight) was injected subcutaneously to the rats at an interval of 24 h for 2 days (9th and 10th day). ISO-induced MI was indicated by the decreased activities of heart creatine kinase and lactate dehydrogenase in rats. ISO administration also enhanced the concentrations of heart mitochondrial lipid peroxidation products and decreased the activities/concentrations of mitochondrial antioxidants, Kreb’s cycle dehydrogenases and mitochondrial electron transport chain complexes I, II?+?III and IV in rats. Furthermore, ISO triggers calcium overload and ATP depletion in the rat’s heart mitochondria followed by the mitochondrial cytochrome-C release and the activation of intrinsic pathway of apoptosis by upregulating the myocardial pro-apoptotic Bax, P⁵³, APAF-1, active caspase-3, active caspase-9 and down regulating the expressions of anti-apoptotic Bcl-2. α-Bisabolol pre and co-treatment showed considerable protective effects on all the biochemical and molecular parameters studied. Transmission electron microscopic study and mitochondrial swelling assay confirmed our biochemical and molecular findings. The in vitro study on hydroxyl radical also revealed the potent free radical scavenging activity of α-bisabolol. Thus, α-bisabolol attenuates mitochondrial dysfunction and intrinsic pathway of apoptosis in ISO-induced myocardial infarcted rats.

     

Alteration in Cytoskeletal Protein Levels in Sciatic Nerve on Post-Treatment of Diisopropyl Phosphorofluoridate (DFP)-Treated Hen with Phenylmethylsulfonyl Fluoride

Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, and a single dose (1.7 mg/kg, sc.) of this compound produces mild ataxia in hens in 7–14 days and a severe ataxia or paralysis (OPIDN) in three weeks. OPIDN is associated with axonal swelling and their degeneration. We have previously observed alteration in neurofilament (NF) protein levels in the spinal cord of DFP-treated hens. The main objective of this investigation was to study NF protein levels in the sciatic nerves (SN) of hens, in which OPIDN has been potentiated by phenylmethylsulfonyl fluoride (PMSF) post-treatment. PMSF is known to protect DFP-treated (1.7 mg/kg) hens from developing OPIDN if injected before, and potentiate OPIDN if injected after the administration of DFP (0.5 mg/kg). The potentiation of OPIDN was accompanied by earlier elevation of NF proteins in the SN particulate fraction. In contrast, SN supernatant fraction showed a transient fall in NF protein levels in potentiation OPIDN. Out of the two other cytoskeletal proteins (i.e., tubulin, tau) studied in this investigation, tubulin also showed earlier elevation in its level in the particulate fraction in potentiated OPIDN. The earlier elevation of NF protein levels in SN particulate fraction in potentiated OPIDN suggested the possible involvement of NFs in delayed neurotoxicity.     

Antihyperglycemic effect of fraxetin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats

Epidemiological studies have demonstrated that the diabetes mellitus is a serious health burden for both governments and healthcare providers. The present study was hypothesized to evaluate the antihyperglycemic potential of fraxetin by determining the activities of key enzymes of carbohydrate metabolism in streptozotocin (STZ) – induced diabetic rats. Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg b.w). Fraxetin was administered to diabetic rats intra gastrically at 20, 40, 80 mg/kg b.w for 30 days. The dose 80 mg/kg b.w, significantly reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) and increased plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as glucokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and hepatic enzymes (aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP)) in the liver tissues of diabetic rats were significantly reverted to near normal levels by the administration of fraxetin. Further, fraxetin administration to diabetic rats improved body weight and hepatic glycogen content demonstrated its antihyperglycemic potential. The present findings suggest that fraxetin may be useful in the treatment of diabetes even though clinical studies to evaluate this possibility may be warranted.     

Mitochondrial Oxidative Stress and Dysfunction in Rat Brain Induced by Carbofuran Exposure

Repeated low-dose exposure to carbofuran exerts its neurotoxic effects by non-cholinergic mechanisms. Emerging evidence indicates that oxidative stress plays an important role in carbofuran neurotoxicity after sub-chronic exposure. The purpose of the present study is to evaluate the role of mitochondrial oxidative stress and dysfunction as a primary event responsible for neurotoxic effects observed after sub-chronic carbofuran exposure. Carbofuran was administered to rats at a dose of 1 mg/kg orally for a period of 28 days. There was a significant inhibition in the activity of acetylcholinesterase (66.6%) in brain samples after 28 days of carbofuran exposure. Mitochondrial respiratory chain functions were assessed in terms of MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) reduction and activity of succinate dehydrogenase in isolated mitochondria. It was observed that carbofuran exposure significantly inhibited MTT reduction (31%) and succinate dehydrogenase activity (57%). This was accompanied by decrease in low-molecular weight thiols (66.6%) and total thiols (37.4%) and an increase in lipid peroxidation (43.7%) in the mitochondria isolated from carbofuran-exposed rat brain. The changes in mitochondrial oxidative stress and functions were associated with impaired cognitive and motor functions in the animals exposed to carbofuran as compared to the control animals. Based on these results, it is clear that carbofuran exerts its neurotoxicity by impairing mitochondrial functions leading to oxidative stress and neurobehavioral deficits.     

Metabolic effect of short term administration of Hoodia gordonii,an herbal appetite suppressant

Hoodia gordonii (family: Apocynaceae) is used traditionally by the Khoi-San tribes to control hunger. It has become extremely popular and has triggered commercial interest due to its appetite suppressant property. The present study was undertaken to investigate the appetite regulatory mechanism and associated metabolic changes induced by the herb. Effect of organic solvent extract of H. gordonii on food intake and body weight of male Sprague Dawley rats was monitored at three different doses 50, 100 and 150 mg/kg body weight, given orally for five days. Subsequently, the dose of 100 mg/kg body weight was selected for further studies on the regulatory hormones and biochemical variables. Dose-dependent reduction in food intake (12–26%) was observed at a dose of 100 and 150 mg/kg body weight (p < 0.05). Appetite suppression persisted for 6 h and food intake was restored within 24 h after stopping of the treatment. There was an increase in liver glycogen stores, activity of mitochondrial CPT-1 and thyroid hormones in treated animals. The circulating levels of NPY and IGF-1 were decreased with marginal increase in leptin and CCK, in case of treated rats. There was no change in blood glucose and insulin levels were not affected significantly. The hormonal and metabolic changes due to treatment with the H. gordonii extract may be responsible for its anorectic activity.     

Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice

Human acatalasemia may be a risk factor for the development of diabetes mellitus. However, the mechanism by which diabetes is induced is still poorly understood. The impact of catalase deficiency on the onset of diabetes has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of diabetogenic alloxan. The incidence of diabetes was higher in acatalasemic mice treated with a high dose (180 mg/kg body weight) of alloxan. A higher dose of alloxan accelerated severe atrophy of pancreatic islets and induced pancreatic β cell apoptosis in acatalasemic mice in comparison to wild-type mice. Catalase activity remained low in the acatalasemic pancreas without the significant compensatory up-regulation of glutathione peroxidase or superoxide dismutase. Furthermore, daily intraperitoneal injection of angiotensin II type 1 (AT1) receptor antagonist telmisartan (0.1 mg/kg body weight) prevented the development of alloxan-induced hyperglycemia in acatalasemic mice. This study suggests that catalase plays a crucial role in the defense against oxidative-stress-mediated pancreatic β cell death in an alloxan-induced diabetes mouse model. Treatment with telmisartan may prevent the onset of alloxan-induced diabetes even under acatalasemic conditions.     

Oral supplementation of standardized extract of Withania somnifera protects against diabetes-induced testicular oxidative impairments in prepubertal rats

Male reproductive dysfunctions and infertility are the common consequences of overt diabetes. Available evidence support oxidative stress to be the underlying mechanism for the manifestation of testicular complications during diabetes. In the present study, we assessed the attenuating effects of Withania somnifera root extract (WS) on diabetes-induced testicular oxidative disturbances in prepubertal rats. Four-week-old prepubertal rats were assigned into nondiabetic control, streptozotocin (STZ)-treated and STZ?+?WS supplemented (500 mg/kg b.w./d, oral, 15 days) groups. Experimental diabetes was induced by a single intraperitoneal injection of STZ (90 mg/kg b.w). Terminally, all animals were killed, and markers of oxidative stress were determined in the testis cytosol and mitochondrial fraction. Severe hyperglycemia and regression in testis size were apparent in diabetic rats. A decline in antioxidant defenses with subsequent elevation in the generation of reactive oxygen species and lipid peroxidation was discernible in testis cytosol and mitochondria of diabetic prepubertal rats, which was significantly reversed by WS. However, there was partial restoration of glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and 3-beta hydroxysteroid dehydrogenase activities in testis of diabetic prepubertal rats administered with WS. Taken together, data accrued suggest the potential of WS to improve diabetes-induced testicular dysfunctions in prepubertal rats.     

Cardioprotective properties of natural medicine in isoproterenol induced myocardial damage in the male Albino rats

The main aim of this study is to investigate cardioprotective properties of natural medicine inmyocardial damage induced male Albino rats. The aqueous extractof Allium sativumwas used for the determination of phenolic compounds and flavonoids. The amount of phenol (1.39 ± 0.37 GAE/g dry weight) and flavonoids (49.1 ± 2.79 QE/g dry weight) were high in aqueous extract. A. sativumextract and showed 68.39 ± 3.6% DPPHscavenging activity. Isoproterenol was used to induce myocardial injury in Albino rats in vivo by subcutaneous injection (100 mg/kg body weight). To achieve this, experimental animals were categorized into six groups (n = 4), namely, positive, negative control, only isoproterenol administered groups, and garlic extract administered group at 100–300 mg extract/kg body weight. Oxidative stress marker and cardiac markers were assayed to analyze the cardioprotective properties of garlic extract. At 300 mg/kg doseof garlic extract, rat was recovered from various altered factors such as, aspartate aminotransferase, alkaline transminase and alkaline phosphatase. The rats treated with 300 mggarlic extract/kg body weight decreased the level of asparate aminotransferase (126 ± 6.4 IU/L) than other lower doses (100 mg extract/kg and 200 mg extract/kg). Alkaline transaminase level of rat serum level was 81 ± 4.34 IU/L. In the isoproterenol treated rats elevated level was observed (152 ± 4.42 IU/L enzyme activity). Pre-treatment of Albino rat with A. sativum extract reduced cardiac damage. Isoproterenol exposed animal showed 207.6 ± 1.2 mg/dL triglyceride and the garlic administered rat (300 mgextract/kg) reduced LDL-cholesterol level (61.3 ± 1.3 mg/dL) significantly (p < 0.05). Creatinine kinase -MB level was 269.5 ± 12.5 IU/L in the control animal and stress induced animal showed elevated level (572.3 ± 19.4 IU/L). Garlic treated experimental animal (300 µg/kg bw) decreased CK-MB level. To conclude, the aqueous extract of A. sativumshowed cardio protective properties against myocardial injury.     

Beneficial effects of DL-alpha-lipoic acid on cyclophosphamide-induced oxidative stress in mitochondrial fractions of rat testis

The present study investigated the protective efficacy of dl-alpha-lipoic acid on the peroxidative damage and abnormal antioxidant levels in the mitochondrial fraction of testis in cyclophosphamide (CP) administered rats. Male Wistar rats of 140+/-20 g were categorized into four groups. Two groups were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce testicular toxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks, 24 h prior to CP administration). A vehicle-treated control group and a lipoic acid drug control group were also included. The mitochondrial fraction of untreated CP-exposed testis showed 1.84-fold increase in lipid peroxidation, along with a significant (P<0.001) increase in hydrogen peroxide levels. In CP-exposed rats, we observed abnormal changes in the activities/levels of mitochondrial enzymic (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non-enzymic (reduced glutathione, ascorbate and alpha-tocopherol) antioxidants. CP-treated rats also showed decline in the activities of mitochondrial enzymes such as succinate dehydrogenase, malate dehydrogenase and isocitrate dehydrogenase. In contrast, rats pretreated with lipoic acid showed normal lipid peroxidation and antioxidant defenses, thereby showing the protection rendered by lipoic acid.