Mahua Sinha

Aqueous extract of Terminalia arjuna prevents carbon tetrachloride induced hepatic and renal disorders

BackgroundCarbon tetrachloride (CCl4) is a well-known hepatotoxin and exposure to this chemical is known to induce oxidative stress and causes liver injury by the formation of free radicals. Acute and chronic renal damage are also very common pathophysiologic disturbances caused by CCl4. The present study has been conducted to evaluate the protective role of the aqueous extract of the bark of Termnalia arjuna (TA), an important Indian medicinal plant widely used in the preparation of ayurvedic formulations, on CCl4 induced oxidative stress and resultant dysfunction in the livers and kidneys of mice.MethodsAnimals were pretreated with the aqueous extract of TA (50 mg/kg body weight) for one week and then challenged with CCl4 (1 ml/kg body weight) in liquid paraffin (1:1, v/v) for 2 days. Serum marker enzymes, namely, glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) were estimated in the sera of all study groups. Antioxidant status in both the liver and kidney tissues were estimated by determining the activities of the antioxidative enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST); as well as by determining the levels of thiobarbutaric acid reactive substances (TBARS) and reduced glutathione (GSH). In addition, free radical scavenging activity of the extract was determined from its DPPH radical quenching ability.ResultsResults showed that CCl4 caused a marked rise in serum levels of GPT and ALP. TBARS level was also increased significantly whereas GSH, SOD, CAT and GST levels were decreased in the liver and kidney tissue homogenates of CCl4 treated mice. Aqueous extract of TA successfully prevented the alterations of these effects in the experimental animals. Data also showed that the extract possessed strong free radical scavenging activity comparable to that of vitamin C.ConclusionOur study demonstrated that the aqueous extract of the bark of TA could protect the liver and kidney tissues against CCl4-induced oxidative stress probably by increasing antioxidative defense activities.

Taurine protects rat testes against NaAsO2-induced oxidative stress and apoptosis via mitochondrial dependent and independent pathways

Arsenic (As) is a well known toxicity inducer. Recent investigations, however, showed that it might have some therapeutic application in cancer treatment. These dual roles of arsenic have attracted a renewed research in organ pathophysiology. In this study, we report that As administration (in the form of NaAsO(2) at a dose of 10mg/kg body weight for 2 days, orally) induces apoptosis in testicular tissue of the experimental rats by the activation of caspase-3 and reciprocal regulation of Bcl-2/Bad with the concomitant reduction of mitochondrial membrane potential and increased level of cytosolic cytochrome C. Arsenite has also been shown to induce activation of mitogen-activated protein kinases (MAPKs), Akt as well as NF-kappaB (p65) in testicular tissue. In addition, As significantly decreased testicular Delta(5)-3beta-HSD and 17beta-HSD activities and reduced the plasma testosterone level, testicular sperm count and sperm motility. Besides, arsenite exposure increased the levels of reactive oxygen species (ROS), serum TNF-alpha, As accumulation and lipid peroxidation and decreased the activities of the antioxidant enzymes and glutathione in the testicular tissue. Oral administration of taurine (at a dose of 100mg/kg body weight for 5 days) was found to be effective in counteracting As-induced oxidative stress, attenuation of testicular damages and amelioration of apoptosis in testicular tissue by controlling the reciprocal regulation of Bcl-2/Bad, phospho-ERK1/2, phospho-p38, phospho-Akt and NF-kappaB. Taurine was also found to play similar beneficial role via mitochondrial dependent pathways in As-induced testicular damages leading to apoptotic cell death.

Protection of arsenic-induced testicular oxidative stress by arjunolic acid

Abstract Arsenic-induced tissue damage is a major concern to the human population. An impaired antioxidant defense mechanism followed by oxidative stress is the major cause of arsenic-induced toxicity, which can lead to reproductive failure. The present study was carried out to investigate the preventive role of arjunolic acid, a triterpenoid saponin isolated from the bark of Terminalia arjuna, against arsenic-induced testicular damage in mice. Administration of arsenic (in the form of sodium arsenite, NaAsO2, at a dose of 10 mg/kg body weight) for 2 days significantly decreased the intracellular antioxidant power, the activities of the antioxidant enzymes, as well as the levels of cellular metabolites. In addition, arsenic intoxication enhanced testicular arsenic content, lipid peroxidation, protein carbonylation and the level of glutathione disulfide (GSSG). Exposure to arsenic also caused significant degeneration of the seminiferous tubules with necrosis and defoliation of spermatocytes. Pretreatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days could prevent the arsenic-induced testicular oxidative stress and injury to the histological structures of the testes. Arjunolic acid had free radical scavenging activity in a cell-free system and antioxidant power in vivo. In summary, the results suggest that the chemopreventive role of arjunolic acid against arsenic-induced testicular toxicity may be due to its intrinsic antioxidant property.

Protective effect of arjunolic acid against arsenic-induced oxidative stress in mouse brain.

Arsenic, a notoriously poisonous metalloid, is ubiquitous in the environment, and it affects nearly all organ systems of animals including humans. The present study was designed to investigate the preventive role of a triterpenoid saponin, arjunolic acid against arsenic‐induced oxidative damage in murine brain. Sodium arsenite was selected as a source of arsenic for this study. The free‐radical‐scavenging activity and the in vivo antioxidant power of arjunolic acid were determined from its 2,2‐diphenyl‐1‐picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of sodium arsenite at a dose of 10 mg/kg body weight for 2 days significantly decreased the activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione‐S‐transferase, glutathione reductase and glutathione peroxidase, the level of cellular metabolites, reduced glutathione, total thiols and increased the level of oxidized glutathione. In addition, it enhanced the levels of lipid peroxidation end products and protein carbonyl content. Treatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days prior to arsenic administration almost normalized above indices. Histological findings due to arsenic intoxication and arjunolic acid treatment supported the other biochemical changes in murine brains. Results of 2,2‐diphenyl‐1‐picryl hydrazyl radical scavenging and ferric reducing/antioxidant power assays clearly showed the in vitro radical scavenging as well as the in vivo antioxidant power of arjunolic acid, respectively. The effect of a well‐established antioxidant, vitamin C, has been included in the study as a positive control. Combining all, results suggest that arjunolic acid possessed the ability to ameliorate arsenic‐induced oxidative insult in murine brain and is probably due to its antioxidant activity.

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 (CdCl(2)) at a dose of 4mg/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 CdCl(2) 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 100mg/kg body weight for 5 days prior to CdCl(2) 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.

Protective role of arjunolic acid in response to streptozotocin-induced type-I diabetes via the mitochondrial dependent and independent pathways

Increasing evidences in both experimental and clinical studies suggest that oxidative stress is involved in the pathogenesis of diabetic tissue damage. Pancreatic beta-cell death is the cause of decreased insulin production in diabetes. Streptozotocin (STZ) is widely used to induce experimental diabetes due to its ability to selectively target and destroy insulin producing pancreatic beta-cells via the formation of both reactive oxygen species (ROS) and RNS (reactive nitrogen species). This study investigated the prophylactic role of arjunolic acid (AA) against STZ-induced diabetes in the pancreas tissue of the Swiss albino rats (as a working model). We observed that STZ administration (at a dose of 65mg/kg body weight, injected in the tail vain) caused increased production of both ROS and RNS in the pancreas tissue of experimental animals. Formation of these reactive intermediates decreased the intracellular antioxidant defense, increased the levels of lipid peroxidation, protein carbonylation, serum glucose and TNF-alpha. Investigating the signaling pathways, we found that STZ administration caused the activation of phospho-ERK1/2, phospho-p38, NF-kappaB and destruction of mitochondrial transmembrane potential, release of cytochrome c as well as activation of caspase 3 in the pancreas tissue keeping the levels of total ERK1/2 and p38 significantly unchanged. Treatment of animals with AA (at a dose of 20mg/kg body weight, orally) both prior and post to the STZ administration effectively reduced these adverse effects by inhibiting the excessive ROS and RNS formation as well as by down-regulating the activation of phospho-ERK1/2, phospho-p38, NF-kappaB and mitochondrial dependent signal transduction pathways leading to apoptotic cell death. Combining all, these results suggest that AA plays some beneficial roles against STZ-induced diabetes.

Cadmium induced testicular pathophysiology: Prophylactic role of taurine

The aim of the present study was to investigate the role of taurine against cadmium induced testicular pathophysiology. Cadmium (in the form of Cadmium chloride, CdCl(2)) administration at a dose of 4 mg/kg body weight for 6 days significantly decreased testicular Delta(5)-3beta-HSD and 17beta-HSD activities along with the reduction in the plasma testosterone level. In addition, reductions in testicular sperm count as well as loss in sperm motility were also observed in Cd-intoxication. Cd increased the intracellular concentration of reactive oxygen species and testicular Cd accumulation. Besides, increased levels of lipid peroxidation, protein carbonylation, glutathione disulfide and DNA fragmentation as well as decreased levels of the activities of the antioxidant enzymes, total thiols and reduced glutathione were also found to be associated with this toxicity. Taurine pretreatment at a dose of 100 mg/kg body weight for 5 days, on the other hand, could prevent all the Cd-induced testicular pathophysiology and oxidative insult related studied parameters. Taurine treatment, in addition also increased the in vivo ferric reducing antioxidant power linearly up to a dose of 100 mg/kg body weight. Histological examination of testicular sections from experimental animals supported these results. The effect of a well established antioxidant, vitamin C has been included in the study as a positive control. Combining all, data suggest that being an antioxidant, taurine plays a beneficial role against Cd-induced adverse effects on the male reproductive system.

Arsenic-induced oxidative cerebral disorders: protection by taurine.

The present study was conducted to investigate whether the conditionally essential amino acid, taurine, could play any protective role against the potent neurotoxin arsenic (As)-induced oxidative impairment in the rat brain. Administration in the form of NaAsO2 (at a dose of 10 mg/kg body weight for 2 days, orally), As increased the intracellular accumulation of metallic As, reactive oxygen species, and super oxide radicals. The toxin also augmented the extent of lipid peroxidation, protein carbonylation, and the levels of glutathione disulphide. Activities of the antioxidant enzymes, membrane-bound enzymes, acetylcholinesterase, and the levels of reduced glutathione, as well as total thiols, have been significantly decreased due to As exposure. Oral administration of taurine (at a dose of 100 mg/kg/body weight for 5 days) was found to be very effective in the prevention of As-induced oxidative impairment in the brain tissue of the experimental rats. To validate the experimental results, a well-known water-soluble antioxidant, vitamin C, was used as the positive control in the study. Combining all, results suggest that taurine plays a beneficial role against As-induced cerebral oxidative stress.

Arjunolic acid attenuates arsenic-induced nephrotoxicity

Arsenic is highly toxic naturally occurring element that affects numerous organ systems in humans. Present study was designed to investigate the preventive role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced nephrotoxicity in mouse model. For this study, NaAsO(2) was chosen as the source of arsenic. Oral administration of NaAsO(2) at a dose of 10mg/kg body weight for 2 days caused significant accumulation of arsenic in renal tissues as well as altered the activities of serum markers, urea nitrogen (UN) and creatinine, antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx), level of cellular metabolites, reduced glutathione (GSH), oxidized glutathione (GSSG) and total thiols, level of lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20mg/kg body weight for 4 days almost normalized above indices. Histological studies also indicated preventive role of AA against NaAsO(2)-induced nephrotoxicity. The radical scavenging activity and in vivo antioxidant power of AA were determined from its DPPH radical scavenging ability and ferric reducing/antioxidant power (FRAP), respectively. A well-known antioxidant, vitamin C was used as positive control throughout the study. Combining all, results suggest that arsenic could cause kidney damage by inducing oxidative stress in mice and that could be prevented by AA.

Prophylactic role of arjunolic acid in response to streptozotocin mediated diabetic renal injury: activation of polyol pathway and oxidative stress responsive signaling cascades.

Diabetic nephropathy is a common cause for end-stage renal disease. Present study investigated the beneficial role of arjunolic acid (AA) against streptozotocin (STZ) induced diabetic nephropathy in rats. Diabetic renal injury was associated with increased kidney weight to body weight ratio, glomerular area and volume, blood glucose (hyperglycemia), urea nitrogen and serum creatinine. This nephro pathophysiology increased the productions of reactive oxygen species (ROS) and reactive nitrogen species (RNS), enhanced lipid peroxidation, protein carbonylation and decreased intracellular antioxidant defense in the kidney tissue. In addition, hyperglycemia activates polyol pathway by increasing aldose reductase (AR) with a concomitant reduction in Na+-K+-ATPase activity. Investigating the oxidative stress responsive signaling cascades, we found the activation of PKCdelta, PKCvarepsilon, MAPKs and NF-kappaB (p65) in the renal tissue of the diabetic animals. Furthermore, hyperglycemia disturbed the equilibrium between the pro and anti-apoptotic members of Bcl-2 family of proteins as well as reduced mitochondrial membrane potential, elevated the concentration of cytosolic cytochrome C and caspase-3 activity. Treatment of AA effectively ameliorated diabetic renal dysfunctions by reducing oxidative as well as nitrosative stress and deactivating the polyol pathways. Histological studies also support the experimental findings. Results suggest that AA might act as a beneficial agent against the renal dysfunctions developed in STZ-induced diabetes.