Evaluation of sublethal cyanide exposure on plasma biochemical profile in rats and possible protective effect of garlic

Introduction Cyanide is a ubiquitous and potent cytotoxic agent known for its rapid lethal action and toxicity. The sources for cyanide poison are diverse, ranging from fruit pits, nuts, or seeds to industrial-based materials, such as those used in metal processing, electroplating, rubber and plastic production, insecticide and rodenticide production, chemical synthesis, and extraction of gold and silver ores. Furthermore, some drugs of medicinal importance, such as Laetrile and Nitroprusside, can release cyanide (Ellenhorn 1997). The toxicity of cyanide is a consequence of its high potency as a respiratory poison in all aerobic forms of life. In addition to acute cyanide intoxication, chronic toxicity has frequently been reported in recent years, and it is suggested that the most widespread problems arising from cyanide are from chronic dietary, industrial and environmental sources (Mathangi & Namasivayam 2000). Cyanide has also been shown to induce oxidative stress and damage in a number of biological systems (Okolie & Iroanya 2003; Okolie & Asonye 2004). It has been reported that prolonged sublethal cyanide exposure can cause biochemical and histopathological alterations in different species (Okolie & Osagie 2000; Sousa et al 2002; Soto-Blanco & Gorniak 2003; Tulsawani et al 2005). Several limitations of commonly available cyanide antidotes (e.g. sodium nitrite, 4-dimethyl aminophenol, sodium thiosulphate, dicobalt edetate, etc.) prompted research for better treatments by new mechanistic based antidotes (Baskin et al 1999; Bhattacharya & Tulsawani 2009; Satpute et al 2010). The conversion of cyanide to thiocyanate is considered to be the main pathway for cyanide detoxification, and is catalysed directly by two sulfurtransferases, rhodanese and 3-mercaptopyruvate sulfurtransferase (Megarbane 2003; Nagahara et al 2003). Rhodanese activity level in catalyzing the transformation of thiosulphate to thiocyanate is limited by the availability of sulfur (Bhatt & Linnell 1987). Experimental sulfur donors have been shown to protect mice against exposure to lethal dose of cyanide (Baskin et al 1999). It has been suggested that sulfur compounds of garlic (Allium sativum) may have a protective effect against cyanide intoxication (Aslani et al 2006; Elsaid & Elkomy 2006). With respect to serious problems resulted from long-term ingestion of low amounts of cyanide, it is important to carefully assess the effects of sublethal doses of cyanide as well as to identify suitable compounds with potential for protecting against resultant tissue damages. So, the present study was undertaken to assess plasma biochemical alterations following sublethal cyanide exposure and also to evaluate the possible protective effect of garlic in cyanide exposed rats. These studies may be of value for further understanding the pathophysiology of cyanide poisoning and as an aid in diagnosis and supportive therapy of long-term exposure to cyanide. Abstract. Three groups of adult male rats (six per group) were used in order to evaluate the effect of prolonged sublethal exposure to potassium cyanide (KCN) on some circulating biochemical indices, and the possible ameliorating effect of garlic on the considered indices. Cyanide administration caused significant (p<0.05) increases in plasma levels of alanine aminotransferase, alkaline phosphatase and urea. On the other hand, plasma levels of aspartate aminotransferase, lactate dehydrogenase, glucose, triglyceride, cholesterol, albumin, total protein, bilirubin and creatinine were not significantly different between the experimental and control groups. The garlic administration modulated the cyanideinduced biochemical alterations, this effect being associated with its organosulfur compounds. Considering both antioxidant properties of garlic organosulfur compounds and their possible ability to elevate the cellular sulfane sulfur level, we suggest garlic as a possible candidate for therapeutic and prophylactic intervention of cyanide poisoning.