Liver and Kidney Lesions and Associated Enzyme Changes Induced in Rabbits by Chronic Cyanide Exposure

doi:10.1016/S0278-6915(99)00059-9

Food and Chemical Toxicology

Volume 37, Issue 7, July 1999, Pages 745-750

https://doi.org/10.1016/S0278-6915(99)00059-9 Get rights and content

Abstract

The effect of prolonged chronic cyanide exposure on liver and kidney integrity, as well as some associated enzyme and metabolite changes, were investigated in New Zealand white rabbits (initial mean weight 1.52 kg) using a combination of colorimetric, spectrophotometric, enzymatic, gravimetric and histological procedures. Two groups of rabbits were fed for 40 weeks on either pure growers’ mash or growers’ mash containing 702 ppm inorganic cyanide. Results obtained indicate that the cyanide-fed rabbits had significantly decreased liver activities of alkaline phosphatase, glutamate pyruvate transaminase and sorbitol dehydrogenase relative to controls (P<0.05). On the other hand, there were significant increases (P<0.05) in the serum activities of these enzymes in the cyanide-treated group. Kidney alkaline phosphatase activity was significantly decreased (P<0.05), while serum urea and creatinine were significantly higher (P<0.05) in the cyanide group relative to controls. The cyanide treatment led to significant increases in both tissue and serum activities of lactate dehydrogenase. In addition, liver and kidney rhodanese activities were significantly raised in the cyanide-fed group. There were marked degenerative changes in the liver and kidney sections from the cyanide-treated rabbits. These results suggest that chronic cyanide exposure may be deleterious to liver and kidney functions.

Introduction

Cyanide is a rapidly acting poison widely used as a suicidal and homicidal agent, as well as in chemical warfare (Yamamoto, 1989). The toxicity of cyanide derives mainly from its potency as a respiratory poison in aerobic organisms. Ingested cyanide is rapidly absorbed from the gastrointestinal tract, and it is a highly potent inhibitor of cytochrome oxidase, with which it reacts to form a stable complex (Buzaleh et al., 1989; Yen et al., 1995). At high doses, death invariably results as a consequence of respiratory failure because the nerve cells of the respiratory centre are highly susceptible to hypoxia (Greer and Jo, 1995). Cassava (Manihot esculenta Crantz) and beans (Vigna unguiculata), two important dietary staples in Nigeria, contain the cyanogenic glucoside linamarin (Nartey, 1981; Okolie and Ugochukwu, 1989; Vanderborght, 1979). Studies on the cyanide contents of these foods in their processed forms have revealed appreciable levels of residual cyanide in cassava (Izokun-Etiobhio and Ugochukwu, 1984) as well as in beans (Okolie and Ugochukwu, 1989). Indeed, cassava toxicity has remained the major thrust of chronic cyanide toxicity studies in the past five decades.

While chronic cyanide toxicity has been unequivocally linked to the aetiology of goitre (Cliff et al., 1986), tropical ataxic neuropathy (Osuntokun, 1981) and epidemic spastic paraparesis (Howlett et al., 1990), not much is known about the possible toxic consequences of cyanide on the liver and kidneys. Although it has been reported that cyanide induced some histopathological derangements in fish liver (Dixon and Leduc, 1981), the data obtained were not correlated with tissue and serum enzyme measurements. In addition, virtually all studies on chronic cyanide toxicity so far have been based on short-term feeding experiments. However, more than 10,000 people in Mozambique, Tanzania and Congo Republic have been paralysed by Konzo, a debilitating disease of sudden onset which arises from prolonged exposure to sublethal levels of dietary cyanide (Shorter, 1997). As chronic cyanide toxicity arises from prolonged ingestion of sublethal doses of cyanide (Nartey, 1978), results obtained from long-term feeding experiments should give more valuable indices for assessing organ damage induced by cyanide.

In the present investigation, the effects of chronic cyanide administration on the integrity of liver and kidney, as well as their associated enzyme changes, were studied using rabbits as animal models.

Section snippets

Animals and feeding

12 Male weanling New Zealand White rabbits (initial mean weight 1.52 kg) aged about 16 wk, were purchased from the animal house, Department of Microbiology, University of Benin. The animals were housed singly in clean metal hutches and acclimatized on growers’ mash (product of Bendel Feed and Flour Mills (BFFM) Ltd, Ewu, Nigeria) for 2 wk prior to the commencement of the experiment. The animals were subsequently divided into two groups, each containing six rabbits. Members of each group were

Results

Table 2 shows feed consumption, weight gains, feed efficiency, thiocyanate output and serum and creatinine levels in the two groups after 40 wk of feeding the respective diets. The cyanide-treated rabbits gained significantly lower (P<0.05) weight than controls, although their feed consumption rate was significantly higher (P<0.05). This was reflected in the inferior feed efficiency of the cyanide feed relative to mash. Urinary thiocyanate as well as serum levels of urea and creatinine were

Discussion

At moderate doses, ingested cyanide is detoxified to thiocyanate by the enzyme rhodanese which is found mainly in the liver (Cerletti, 1986). Thus, cyanide toxicity is usually associated with elevated urinary thiocyanate levels (Delange et al., 1980; Cassadei et al., 1986). The higher levels of liver and kidney rhodanese activities in the cyanide-fed rabbits are consistent with the much higher output of urinary thiocyanate in this group. However from results of histology and enzyme assays, it

Acknowledgements

We appreciate the assistance of Mr E. Woghiren of the Department of Anatomy, Faculty of Medicine, University of Benin, and Mr S. Keshi of the Department of Morbid Anatomy, University of Benin Teaching Hospital, in preparing the tissue samples for light microscopy. Many thanks also to Dr Tunde Diegbe, Histopathologist and Lecturer, Faculty of Medicine, University of Benin, for reading and interpreting the slides. Finally, we are indebted to Dr (Mrs) Airauhi of the Department of Morbid Anatomy

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Research SectionLiver and Kidney Lesions and Associated Enzyme Changes Induced in Rabbits by Chronic Cyanide Exposure

Abstract

Introduction

Section snippets

Animals and feeding

Results

Discussion

Acknowledgements

General Pharmacology

Trends In Biochemical Sciences

Food Chemistry

Toxicology and Applied Pharmacology

American Journal of Emergency Medicine

The usefulness of the enzymatic tests in acute poisonings

Archives of Toxicology

Evidence that cassava ingestion increases thiocyanate formation: a possible etiologic factor in endemic goitre

Journal of Clinical Endocrinology and Metabolism

The determination of thiocyanate in blood serum

Biochemical Journal