Biochemical and Histopathological Alterations in Different Tissues of Rats Due to Repeated Oral Dose Toxicity of Cymoxanil

Abstract

Evaluating potential adverse health impacts caused by pesticides is an important parameter in human toxicity. This study focuses on the importance of subchronic toxicity assessment of cymoxanil fungicide in rats with special reference to target biochemical enzymes and histopathological changes in different tissues. In this regard, a 21-day toxicity study with repeated cymoxanil oral doses was conducted. It has been shown that low doses (0.5 mg/kg) were less effective than medium (1 mg/kg) and high (2 mg/kg) doses. Moreover, high dose dose-treated rats showed piecemeal necrosis in the liver, interstitial nephritis and tubular degeneration in the kidneys, interstitial pneumonia and type II pneumocyte hyperplasia in the lungs, gliosis, spongiosis, and malacia in the brain, and testicular edema and degeneration in the testes. Cymoxanil significantly increased AST, ALT, and ALP in serum and liver, indicating tissue necrosis and possible leakage of these enzymes into the bloodstream. Creatinine levels increased, indicating renal damage. Similarly, significant inhibition was recorded in brain acetylcholinesterase, indicating that both synaptic transmission and nerve conduction were affected. Importantly, these histopathological and biochemical alterations were dose-dependent. Taken together, our study reported interesting biochemical and histopathological alterations in different rat tissues following repeated toxicity with oral doses of cymoxanil. Our study suggests future studies on different pesticides at different concentrations that would help urge governments to create more restrictive regulations concerning these compounds' levels.

Keywords: ALP; ALT; AST; brian; cholinesterase; cymoxanil; liver; rats; testes.

Figure 1

Effect of cymoxanil on the liver. (A) Liver of rat treated with low and medium dose showing congestion (arrow) and dilation of the hepatic sinusoids (H&E, bar = 50 µm). (B) Liver of rats treated with low and medium dose showing focal hepatocytic necrosis (arrow) with moderate infiltration of mononuclear cells (H&E, bar = 50 µm). (C) Liver of rats treated with high dose showing hemorrhages (arrow) (H&E, bar = 50 µm). (D) Liver of rats treated with high dose showing extensive piecemeal necrosis (arrow) with infiltration of mononuclear cells within and at the margin of the necrosed areas (H&E, bar = 50 µm). (E) Liver of control rats showing hepatic sinusoids in between hepatic cords and they are arranged around central vein (H&E, bar = 50 µm).

Figure 2

Effect of cymoxanil on the kidneys. (A) Kidneys of rats treated with low and medium dose showing slight interstitial nephritis (triangle) with intertubular infiltration of mononuclear cells and degeneration of renal tubule epithelial lining (H&E, bar = 50 µm). (B) Kidneys of rats treated with high dose showing severe interstitial nephritis (triangle) and dilatation of the adjacent renal tubules (arrow) (H&E, bar = 100 µm). (C,D) Kidneys of rats treated with high dose showing thickening and sclerosis of the Bowman capsule and the surrounding renal tubules (arrows) (H&E and PAS respectively, bar = 50 µm). (E) Kidneys of control rats showing renal tubules with intact lining epithelium and glomeruli (H&E, bar = 50 µm).

Figure 3

Effect of cymoxanil on the brain. (A) Brain of rats treated with medium dose showing perivascular cuff (arrows) (H&E, bar = 50 µm). (B) Brain of rats treated with medium dose showing slight gliosis (arrow) (H&E, bar = 50 µm). (C) Brain of rats treated with high dose showing cerebral spongiosis (arrow) (H&E, bar = 50 µm). (D) Brain of rats treated with high dose showing cerebral malacia (arrow) (H&E, bar = 50 µm). (E) Brain of control showing intact neuronal cells and blood vessels surrounded with clear perivascular space in the neuropil of cerebrum (H&E, bar = 50 µm).

Figure 4

Effect of cymoxanil on the lungs and testis. (A) Lungs of rats treated with medium dose showing thickening of the inter-alveolar septa (triangle) (H&E, bar = 50 µm). (B) Lungs of rats treated with high dose showing massive interstitial pneumonia (triangle) with pneumocyte type II hyperplasia (arrows) (H&E, bar = 50 µm). (C) Testis of rats treated with medium dose showing decrease in the number of spermatogenic layers (triangle) with slight and focal interstitial oedema (star) (H&E, bar = 50 µm). (D) Testis of rats treated with high dose showing complete necrosis of the lining epithelium of some seminiferous tubules (triangle) and massive interstitial oedema (star) (H&E, bar = 100 µm). (E) Lungs of control rats showing clear alveoli and small interalveolar septa (H&E, bar = 50 µm). (F) Testis of control rats showing spermatogenic cells arranged in layers with mature spermatozoa (H&E, bar = 50 µm).