Maneb disturbs expression of superoxide dismutase and glutathione peroxidase, increases reactive oxygen species production, and induces genotoxicity in liver of adult mice

Abstract

Maneb (MB), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. However there is a lack of informations regarding the risks arising from MB exposure on non target organisms, especially mammals. The aim of this study was to investigate the morphological, biochemical and molecular aspects of liver injury after exposure of mice to MB. Four doses of MB corresponding to 1/8 (group D1), 1/6 (group D2), 1/4 (group D3), and 1/2 (group D4) of lethal dose (DL50 = 1500 mg/kg body weight) were administered to adult mice. Oxidative stress parameters were also objectified by molecular and histological endpoints in the liver. Maneb caused hepatotoxicity as characterized by the significant increase in the levels of malondialdehyde and protein oxidation marker, advanced oxidation protein products (AOPP). The activities of catalase, glutathione peroxidase, superoxide dismutase and the levels of glutathione decreased significantly in all treated mice, while vitamin C levels decreased only in group D4. We also noted a significant decrease in gene expression of superoxide dismutase and glutathione peroxidase enzymes. Maneb caused nucleic acids degradation testifying its genotoxicity. Yet, biochemical markers in plasma showed a decrease in total protein and an increase in aspartate, alanine amino transferases and bilirubin levels in all treatment groups. Moreover, plasma levels of cholesterol, triglycerides and low density lipoprotein-cholesterol significantly increased, while those of high density lipoprotein-cholesterol decreased. These biochemical alterations were correlated with significantly histological changes. Our data showed, for the first time, that intraperitoneal injection of very high non environmentally relevant MB concentrations to adult mice resulted in oxidative stress leading to hepatotoxicity and the impairment of defense systems, confirming the pro-oxidant and genotoxic effects of this fungicide.

Beneficial role of vanillin, a polyphenolic flavoring agent, on maneb-induced oxidative stress, DNA damage, and liver histological changes in Swiss albino mice

“…Reciprocally, SOD protected CAT against inhibition by superoxide anion that could be formed during maneb treatment. Our results were in agreement with the study of Ben Amara et al, 23 who have observed a significant decrease in the activities of CAT and SOD in the liver of adult mice exposed to graded doses of maneb. The significant recovery of hepatic antioxidant enzyme activities by vanillin suggested its chemopreventive effect against maneb-mediated hepatic injury.…”

“…Our results were in agreement with the study of Rajeswary et al, 40 who have observed no changes in the BW of rats treated orally with carbendazim fungicide (25 mg kg −1 BW) for a long period (48 days). While a significant loss has been found by Ben Amara et al, 23 in BW of mice treated with graded high doses of maneb (1/8, 1/6, 1/4, and 1/2 of LD50) during 7 days, which may occur as a result of severe acute maneb toxicity. In our study, we have used a maneb dose of 30 mg kg −1 BW, representing (1/50 of LD50) which is the lower than the doses tested by Ben Amara et al 23 On the other hand, the marked increase in liver weight, recorded in maneb group, could be a result of the hepatic inflammation caused by maneb, as confirmed by our histological findings.…”

“…While a significant loss has been found by Ben Amara et al, 23 in BW of mice treated with graded high doses of maneb (1/8, 1/6, 1/4, and 1/2 of LD50) during 7 days, which may occur as a result of severe acute maneb toxicity. In our study, we have used a maneb dose of 30 mg kg −1 BW, representing (1/50 of LD50) which is the lower than the doses tested by Ben Amara et al 23 On the other hand, the marked increase in liver weight, recorded in maneb group, could be a result of the hepatic inflammation caused by maneb, as confirmed by our histological findings. Our results were similar to those previously obtained by Razia and Siddiqui, 41 where a remarkable increase in liver weight of mice treated for 4 weeks with mancozeb fungicide (2.4 and 6.4 mg kg −1 BW) has been found.…”

“…Despite its apparent low toxicity, numerous in vitro and in vivo studies have confirmed that maneb exposure causes lipid peroxidation, reactive oxygen species (ROS) generation, and alterations in antioxidant defense systems, as a result of complex III inhibition in mitochondrial electron transport chain. 17 –22 According to Ben Amara et al, 23 maneb, used at graded doses (1/8, 1/6, 1/4, and 1/2 of LD50), is able to generate free radicals in the liver of adult mice, leading to an impairment of liver defense system. Moreover, maneb increases the prevalence of Parkinson’s disease in humans 18 and in laboratory rodents.…”

Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants

“…Other pyrethroid pesticides also exhibit pro-oxidative properties in the liver, as shown in Table 3 [367][368][369][370][371], and various organophosphorus and organochlorine insecticides cause oxidative stress in animal liver [136,183,371,372]. Furthermore, several studies have reported the pro-oxidative properties of some herbicides [151,153,154,221,[373][374][375][376] and chemical families of fungicides (carbamate, benzimidazole, strobilurin, azoles, triazoles [159,[377][378][379][380][381][382][383]) (Table 3). Liver oxidative stress is also reported in animals exposed to a mixture of pesticides [168,193,384] (Tables 1 and 3).…”