Protection against salicylate-induced hepatic injury by zinc. A histochemical and biochemical study

Abstract

Female Wistar rats received an oral dose of 700 mg salicylic acid/kg body wt., given as sodium salicylate. Some of the salicylate-treated rats received two subcutaneous injections of 100 mumol kg-1 ZnCl2 (24 h before and simultaneously with the salicylate administration). Other animals were given one subcutaneous injection of 100 mumol kg-1 ZnCl2 simultaneously with the salicylate treatment. Control rats were similarly injected with ZnCl2. Twenty four hours after salicylate treatment, serum and livers were taken for histochemical and biochemical analysis. The most remarkable effects of the treatment were enrichment of lipid droplets and iron and a reduction of glycogen, particularly in the periportal hepatocytes. The effects of salicylate were partially prevented by two ZnCl2 injections. The protective effects of ZnCl2 may be due to lower iron uptake into hepatocytes and by the induction of zinc metallothionein, which can serve as a scavenger for oxygen radicals.

Changes in hepatic gene expression in response to hepatoprotective levels of zinc

“…The hepatoprotective dose for ZnCl 2 was selected based on the literature (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), and a commonly used dose of Zn (100 mmol/kg) was injected s.c. to mice in a volume of 10 ml/kg, or to rats in a volume of 2 ml/kg, once per day in the morning for four consecutive days. Control animals were injected with the same volume of vehicle (saline).…”

“…Zn treatment reduces the hepatotoxicity produced by a wide variety of diverse agents such as carbon tetrachloride (5), bromobenzene (6), thioacetamide (7), ethanol (8), d ‐galactosamine (9), endotoxin (10), d ‐galactosamine plus lipopolysaccharides or tumour necrosis factor (TNF)‐α (11). Zn pretreatment also decreases liver injury produced by drug overdose, such as acetaminophen (12, 13), salicylate (14) and cisplatin (15). Zn is also well known to protect against hepatotoxicity of metals, such as cadmium (16), mercury (17), arsenic (18), nickel (19) and copper (20).…”

Toxicological Profile for Zinc

“…Pretreatment with zinc has been shown to reduce hepatotoxicity induced by xenobiotics such as acetaminophen, bromobenzene, carbon tetrachloride, D-galactosamine, gentamicin, and salicylate (Cagen and Klaassen 1979;Gunther et al 1991;Hu et al 1992;Szymanska et al 1991;Yang et al 1991). The protective effect of zinc against carbon tetrachloride toxicity is dose dependent at high dose levels of zinc, probably because of sequestering of toxic metabolites of carbon tetrachloride by metallothionein (Cagen and Klaassen 1979).…”

“…Zinc may be elevating NADPH (nicotinamide adenine dinucleotide phosphate) content in the cell, resulting in regeneration of glutathione, which increases the antioxidative ability of hepatic cells. Salicylate-induced hepatic alterations (increased lipid droplets and iron, reduced glycogen) (Gunther et al 1991) and gentamicin-induced proximal tubular necrosis (Yang et al 1991) were diminished in rats pretreated with injections of zinc chloride and zinc sulfate, respectively.…”

ATSDR evaluation of the health effects of zinc and relevance to public health

“…Pretreatment with zinc has been shown to reduce hepatotoxicity induced by xenobiotics such as acetaminophen, bromobenzene, carbon tetrachloride, d-galactosamine, gentamicin, and salicylate (Cagen and Klaassen, 1979;Gunther et al, 1991;Szymanska et al, 1991;Yang et al, 1991;Hu et al, 1992). The protective effect of zinc against carbon tetrachloride toxicity is dose dependent at high dose levels of zinc, probably because of sequestering of toxic metabolites of carbon tetrachloride by metallothionein (Cagen and Klaassen, 1979).…”