• Journal of Veterinary Clinics
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• v.25 no.6
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• pp.510-513
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• 2008

Two dogs were referred due to vomiting, depression and anorexia after ingestion of xylitol gum. Both dogs were presented with hepatic failure and one dog had concurrent renal failure. Aggressive supportive treatment was performed, but these dogs died. Necropsy of one dog revealed acute hepatic necrosis, severe renal damages, and hemoperitoneum. This case report demonstrates potential hazard of xylitol toxicity for dogs with clinicopathological and pathological findings.

• BMB Reports
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• v.40 no.6
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• pp.1039-1049
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• 2007

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.

• BMB Reports
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• v.40 no.3
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• pp.382-395
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• 2007

The herb, Cajanus indicus L, is well known for its hepatoprotective action. A 43 kD protein has been isolated, purified and partially sequenced from the leaves of this herb. A number of in vivo and in vitro studies carried out in our laboratory suggest that this protein might be a major component responsible for the hepatoprotective action of the herb. Our successive studies have been designed to evaluate the potential efficacy of this protein in protecting the hepatic as well as renal tissues from the sodium fluoride (NaF) induced oxidative stress. The experimental groups of mice were exposed to NaF at a dose of 600 ppm through drinking water for one week. This exposure significantly altered the activities of the antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and the cellular metabolites such as reduced glutathione (GSH), oxidized glutathione (GSSG), total thiols, lipid peroxidation end products in liver and kidney compared to the normal mice. Intraperitoneal administration of the protein at a dose of 2 mg/kg body weight for seven days followed by NaF treatment (600 ppm for next seven days) normalized the activities of the hepato-renal antioxidant enzymes, the level of cellular metabolites and lipid peroxidation end products. Post treatment with the protein for four days showed that it could help recovering the damages after NaF administration. Time-course study suggests that the protein could stimulate the recovery of both the organs faster than natural process. Effects of a known antioxidant, vitamin E, and a non-relevant protein, bovine serum albumin (BSA) have been included in the study to validate the experimental data. Combining all, result suggests that NaF could induce severe oxidative stress both in the liver and kidney tissues in mice and the protein possessed the ability to attenuate that hepato-renal toxic effect of NaF probably via its antioxidant activity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.2
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• pp.249-257
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• 2010

Crataegii Fructus is commonly used as a improving digestion, removing retention of food, promoting blood circulation and resolving blood stasis agent in East Asia. Cadmium (Cd) is widely distributed in the environment due to its use in industry. An exposure to Cd causes dysuria, polyuria, chest pain, hepatic and renal tubular diseases. The liver is the most important target organ when considering Cd-induced toxicity because Cd primarily accumulates in the liver. This study investigated the protective effect of Crataegii Fructus water extract against cadmium ($CdCl_2$, Cd)-induced liver toxicity in H4IIE cells, a rat hepatocyte-derived cell line and in rats. Cell viability was significantly reduced in Cd-treated H4IIE cells in a time and concentration-dependent manner. However, Crataegii Fructus water extract (CFE) protected the cells from Cd-induced cytotoxicity via inhibition of PARP cleavage. To induce acute toxicity in rats, Cd (4 mg/kg body weight) was dissolved in normal saline and intravenously injected into rats. The rats then received either a vehicle or silymarin (as a positive control) or CFE (50, 100 mg/kg/day) for 3 days, and were subsequently exposed to a single injection of Cd. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly increased by Cd treatment. In contrast, pretreatment with CFE reduced ALT, AST and LDH. In histopathological analysis, CFE reduced the hepatic degenerative regions and the number of degenerative hepatocytes. These are considered as direct evidences that Crataegii Fructus has favorable inhibitory effects on the Cd-intoxicated liver damages. The efficacy of Crataegii Fructus shows slight lower than that of silymarin in the present study.