metallothionein and kutkin

Cadmium (Cd), an industrial and environmental pollutant, is toxic to several tissues, most notably causing hepatotoxicity on acute administration and nephrotoxicity following chronic exposure. The therapeutic efficacy of Picroliv--a standardized fraction of Picrorhiza kurroa, was investigated in male rats treated with Cd as CdCl2 (0.5 mg/kg, sc) 5 days/week for 24 weeks and Picroliv at two doses (6 and 12 mg/kg, p.o.) was given during the last 4 weeks. The Cd induced levels of malondialdehyde and membrane fluidity and decreased levels of non protein sulphydryls and Na+K+ATPase activity of hepatic tissue, along with liver function serum enzymes were restored to near normalcy on treatment with the higher dose of Picroliv. Enhanced excretion of urinary proteins, Cd, Ca and enzymes (lactate dehydrogenase and N-acetyl-beta-D-glucosaminidase) evident at 24 weeks of Cd exposure, indicated severe renal damage. Picroliv appeared less effective in causing restoration of these urinary parameters as well as oxidative stress indices in the renal tissue. Picroliv not only reduced the accumulated levels of Cd, Zn and Ca and Cd-metallothionein in liver, but also enhanced the bile flow and biliary Cd. The morphological alterations in liver caused by Cd appeared less marked on Picroliv treatment. However, the renal morphology remained uninfluenced. Our earlier data on 18 weeks of Cd and 4 weeks of Picroliv co-treatment showed significant amelioration of both hepatic and renal manifestations of Cd. The hepatic protection by Picrilov is clearly demonstrated in this study, while marginal lowering of urinary proteins and enzymes is a positive signal of renal protective efficacy of Picroliv, which could be augmented by adopting higher doses and extended regimen.

Topics: Animals; Cadmium; Calcium; Cinnamates; Glycosides; Lipid Peroxidation; Liver; Male; Membrane Fluidity; Metallothionein; Plant Extracts; Rats; Sodium-Potassium-Exchanging ATPase; Vanillic Acid

The therapeutic efficacy of Picroliv--a standardized extract of Picrorhiza kurroa--was investigated in male rats exposed to CdCl2 (0.5 mg/kg, sc), 5 days/week for 18 weeks. Picroliv at two doses (6 and 12 mg/kg, po) was given to the cadmium (Cd)-administered group for the last 4 weeks (i.e., weeks 15-18). The Cd altered oxidative stress indices, such as increased lipid peroxidation and membrane fluidity, reduced levels of non-protein sulphydryls (NPSHs), and Na+K+ATPase activity in the liver and kidney were found close to the control values by Picroliv treatment, suggesting its antioxidant potential. The hepatoprotective action of Picroliv was evident by its ability to lower the Cd-induced liver function parameters--the serum enzymes, such as alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT) and lactate dehydrogenase (LDH). Bile flow and biliary Cd also increased as a result of Picroliv's choleretic property. The Cd-induced serum urea and urinary excretion of proteins, calcium (Ca), Cd and enzymes, such as N-acetyl-beta-D-glucosaminidase (NAG) and LDH, were less marked on Picroliv treatment, indicating recovery from nephrotoxicity. Organ uptake of Cd and essential metals by Cd exposure was reduced on Picroliv treatment. Cd-induced hepatic metallothionein (MT) was lowered by Picroliv, whereas renal MT was unaltered. Cd-induced hepatic damage was also minimized. However, the renal morphological changes were marginally protected by Picroliv. The 12-mg Picroliv dose was more effective than the 6-mg dose in causing amelioration of the above parameters. This study has provided clear evidence for the hepato- and renal protective efficacy of Picroliv against experimental Cd toxicity.

Topics: Animals; Bile; Cadmium; Calcium; Cinnamates; Glycosides; Kidney; Lipid Peroxidation; Liver; Male; Membrane Fluidity; Metallothionein; Rats; Sodium-Potassium-Exchanging ATPase; Vanillic Acid