Sadhana Shrivastava

Therapeutic potential of thymoquinone against anti-tuberculosis drugs induced liver damage.

Hepatotoxicity is the most serious adverse effect related to tuberculosis treatment which interrupts the successful completion of tuberculosis treatment. The purpose of this study was to assess therapeutic effect of thymoquinone (TQ) against anti-tuberculosis drugs (ATD) induced liver damage. Rats were treated with ATD for 8 weeks (3 days/week) as given for the treatment of TB. This was followed by therapy of TQ for 8 weeks (3 days/week). Administration of combined ATD induced hepatotoxicity was evident from a significant elevation in the AST, ALT, ALP, bilirubin, albumin, cholesterol, urea, uric acid, creatinine, LPO and decreased activities of enzymes. These altered variables were significantly reversed toward control after treatment with TQ. Histological studies also supported biochemical findings. Results of this study strongly indicated protective effect of TQ and thus, can be expected as promising protective agent in maintenance of normal hepatic function during treatment with ATD.

Emodin reverses CCl4 induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural changes: The in vivo evidence

Aim:  The curative effect of emodin (1,3,8‐trihydroxy‐6‐methyl anthraquinone), an active compound of the plant species Ventilago maderaspatana Gaertn, was evaluated against carbon tetrachloride (CCl4) induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural alterations in rats.

Role of micronutrients against dimethylmercury intoxication in male rats.

Mercury is one of the most toxic non-radioactive heavy metals. Chelation therapy has been the basis for the medical treatment of mercury poisoning. Male albino rats were administered dimethylmercury (1.5mg/kg) orally for 21 days. Chelation therapy with N-acetyl cysteine along with combination of antioxidants viz. zinc and selenium was given for 5 days after 24h of toxicant administration. All animals were sacrificed after 48h of last treatment and various blood biochemical parameters were performed. Toxicant caused rise in bilirubin, γ-GT, cholesterol, triglycerides, urea, creatinine, the uric acid content with a decline in albumin. A significant elevation was observed in LPO content and mercury concentration, along with concomitant decline in GSH levels after toxicant administration in liver, kidney and brain. Noticeable fall was also observed in AChE enzyme. Histopathological analysis was consistent with the biochemical observations and led to conclude that combination therapy provided protection against mercury toxicity.

Evaluation of the antioxidant and hepatoprotective effect of Majoon-e-Dabeed-ul-ward against carbon tetrachloride induced liver injury

The present study was designed to demonstrate the antioxidant and hepatoprotective effect of Majoon-e-Dabeed-ul-ward, a Unani herbal formulation. The Majoon-e-Dabeed-ul-ward (MD) at the doses of 250, 500 and 1000 mg/kg, p.o. was administered after carbon-tetrachloride (CCl(4); 1.5 ml/kg, i.p. once only) intoxication. Treatment with MD at three doses brought the levels of aspartate transaminase, alanine transaminase, albumin and urea in dose dependent manner. Signification reduction was found in TBARS content and restored the level of reduced glutathione, adenosine triphosphatase, and glucose-6-phosphatase in liver. Therapy of MD showed its protective effect on biochemical and histopathological observation at all the three doses in a dose dependent manner. The study conducted showed that MD possesses strong hepatoprotective activity as decrease the hexobarbitone sleep time and improvement in physiological parameter, excretory capacity (BSP retention time) was seen. DPPH and H(2)O(2) scavenging effects indicated its potent antioxidant activities. The results revealed that MD could afford significant dose-dependent protection against CCl(4) induced hepatocellular injury.

Combined effect of HEDTA and selenium against aluminum induced oxidative stress in rat brain.

Aluminium (Al) is a potent neurotoxin and has together with other metals been suggested to be associated with Alzheimers disease causality. The current study was carried out to investigate the potential role of N(2-hydroxyethyl) ethylenediamine triacetic acid (HEDTA) and Se in combination against Al induced toxicity. Animals were exposed to Al at a dose of 27 mg/kg/d i.p. for 60 days. HEDTA and Se were administered at a dose of 20mg/kg/d i.p. and 0.5mg/kg/d orally, respectively for 7 consecutive days. Induction of oxidative stress was recorded in the brain after Al exposure. Significant decrease was found in the levels of reduced glutathione activities of the enzymes glutathione reductase, glutathione peroxidase, catalase, superoxide dismutase, acetyl cholinesterase, and increased levels were observed in LPO and glutathione-S-transferase activity in brain and serum. These parameters responded positively to therapy with HEDTA, but more pronounced beneficial effects were observed when HEDTA was administered in combination with Se. The combination was effective in reducing the concentration of Al and level of DNA damage.

Hepatic endogenous defense potential of propolis after mercury intoxication

Exposure to mercuric chloride (HgCl(2) ; 5 mg kg(-1) body weight; i.p.) induced oxidative stress in mice and substantially increased lipid peroxidation (LPO) and oxidized glutathione (GSSG) levels, decreased the level of reduced glutathione (GSH) and various antioxidant enzymes in liver and also increased the activities of liver marker enzymes in serum. Therapy with propolis extract, a resinous wax-like beehive product (200 mg kg(-1) orally, after mercury administration), for 3 days inhibited LPO and the formation of GSSG and increased the level of GSH in the liver. Release of serum transaminases, alkaline phosphatase, lactate dehydrogenase and γ-glutamyl transpeptidase were significantly restored after propolis treatment. The activities of antioxidant enzymes, that is, superoxide dismutase, catalase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase, were also concomitantly restored towards normal levels after propolis administration. These observations clearly demonstrate that propolis treatment augments antioxidant defense against mercury-induced toxicity and provide evidence that propolis has therapeutic potential as a hepatoprotective agent.

Bougainvillea spectabilis Exhibits Antihyperglycemic and Antioxidant Activities in Experimental Diabetes

The study investigates the effects of aqueous extract of Bougainvillea spectabilis leaves on blood glucose, glycosylated hemoglobin, lipid profile, oxidative stress, and on DNA damage, if any, as well as on liver and kidney functions in streptozotocin-induced diabetes in Wistar rats. Daily administration of the aqueous extract of B spectabilis leaves for 28 days resulted in significant reduction in hyperglycemia and hyperlipidemia as evident from restoration of relevant biochemical markers following extract administration. The extract also exhibited significant antioxidant activity as evidenced from the enzymatic and nonenzymatic responses and DNA damage markers. The extract restored kidney and liver functions to normal and proved to be nontoxic. A marked improvement in the histological changes of tissues was also observed. The present study documented antihyperglycemic, antihyperlipidemic, and antioxidative potentials of the aqueous extract of B spectabilis leaves without any toxicity in streptozotocin-treated Wistar rats.

Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats

Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50μg/kg, 100μg/kg, 150μg/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies.

Therapeutic potential of quercetin against acrylamide induced toxicity in rats.

Acrylamide (AA) is found in foods containing carbohydrates and proteins, where it is formed during the heating process. It is classified as neurotoxic and probably carcinogenic to humans. The present investigation was aimed to determine the lethal Dose (LD50) of AA and to evaluate the protective effects of quercetin (QE) against AA induced adverse effects in rats. For the determination of LD50, AA was administered orally at four different doses (46.4mg/kg, 100mg/kg, 215mg/kg and 464mg/kg) to experimental animals for seven days. After 7days LD50 of AA was determined using graphical method of Miller and Tainter. Then AA was administered at 1/3rd dose of LD50 (38.27mgkg-1 body weight; p.o. for 10 days) followed by the therapy of QE (5, 10, 20 and 40mg kg-1 orally), for 3 consecutive days for the determination of protective effect of QE against AA. The estimated LD50 of AA was 114.81mg/kg with 95% confidence interval. Exposure to AA 1/3rd dose of LD50 for 10days induced neurotoxicity which was confirmed by decreased acetylcholinesterase (AChE) activity. AA substantially increased lipid peroxidation (LPO), decreased the level of reduced glutathione (GSH) and antioxidant enzymes (SOD and CAT) in liver, kidney and brain. It also increased the activities of serum transaminases, urea, uric acid, creatinine, lipid profile, bilirubin in serum. Treatment with QE restored tissue and serological indices concomitantly towards normal levels. These results revealed that QE is able to significantly alleviate the toxicity induced by AA in rats.

Therapeutic associated with occupational exposure to silica

Occupational exposure to silica dust has been increasing the possible risk of varieties of pathologies. The aim of this study was to evaluate the protective activity of ethanolic extract of Glycyrrhiza glabra roots at doses of 500 and 1000 mg/kg, p.o., given for 7 days against the toxicity of SiO(2) nanoparticles (50mg/kg intraperitoneal for 6 weeks) in rats. Exposure to silica altered various respiratory and biochemical variables, including ALT, AST, albumin, urea, uric acid, creatinine, catalase, LPO and GSH. Treatments with G. glabra extract significantly improved antioxidant status towards control. Stone workers in the Gwalior region exposed to silica dust had higher prevalence of cough, wheezing and shortness of breath. Increased serum ACE level was noted in the silica exposed group. It is of immense need to monitor this problem for betterment of workers health.