Protective effect of melatonin against herbicides-induced hepatotoxicity in rats

Abstract

Exposure to the herbicides Paraquat and Roundup® may cause cell lesions due to an increase in oxidative stress levels in different biological systems, even in the liver. The aim of this study was to analyze the effect of melatonin on liver of rats exposed to herbicides. A total of 35 rats were randomly divided into seven equal-sized groups: control, Paraquat, Roundup®, Paraquat + Roundup®, Paraquat + melatonin, Roundup® + melatonin, and Paraquat + Roundup® + melatonin. Samples of blood and hepatic tissue were collected at the end of the seventh day of exposure and treatment with melatonin. Body weight, hematological parameters, and histopathological, biochemical analyses and determination of oxidative stress levels in liver were evaluated. Body weight was compromised (P < 0.01). Alterations of hematologic parameters were significant when compared to control (P < 0.001). Biochemically, serum levels of albumin decreased (P < 0.001), but serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased (P < 0.001). Histopathology revealed necrotic hepatocytes, portal and central-lobular inflammatory infiltrate, congestion of capillaries. Serum levels of thiobarbituric acid reactive substances were found to be significantly elevated (P < 0.05; P < 0.001), and serum level of reduced glutathione was significantly lower (P < 0.05; P < 0.001). The groups treated concomitantly with melatonin revealed results similar to those of the control. However, melatonin acted as a protective agent for the liver against experimentally induced hepatic toxicity, promoting prevention of body weight, oxidative stress, and normalization of hematological and biochemical parameters.

Therapeutic benefit of melatonin in 5‐fluorouracil‐induced renal and hepatic injury

“…Studies have confirmed that MEL can also protect the liver and kidney and enhance the antioxidant protective effects of chemotherapy drugs like cisplatin and adriamycin 30–32 . In similar studies, the antioxidant properties, suppression of inflammatory response and apoptosis of MEL against toxicity caused in the liver by cadmium, cyclosporine and herbicides have been observed 33–36 . Also, similar studies have measured its protective properties in the kidney tissue against toxicity caused by aluminium, lead and similar protective properties 36,37 .…”

“…[30][31][32] In similar studies, the antioxidant properties, suppression of inflammatory response and apoptosis of MEL against toxicity caused in the liver by cadmium, cyclosporine and herbicides have been observed. [33][34][35][36] Also, similar studies have measured its protective properties in the kidney tissue against toxicity caused by aluminium, lead and similar protective properties. 36,37 Considering the toxic effects of 5-FU as well as the protective properties of MEL observed in previous studies, our study was conducted to investigate the protective effects of MEL against hepatotoxicity and renal toxicity caused by 5-FU in male rats.…”

Roles of oxidative stress/JNK/ERK signals in paraquat-triggered hepatic apoptosis

“…Similar to the lungs, the liver is a hallmark target organ of systemic PQ poisoning ( Hong et al, 2000 , Spangenberg et al, 2012 ). Epidemiological and animal experimental data have shown hepatotoxic characteristics (including abnormal liver function and pathological liver injury) after PQ exposure in humans and mammals ( Almeida et al, 2021 , Deveci et al, 1999 , Hong et al, 2000 , Takegoshi et al, 1988 ). However, few studies have investigated the molecular mechanisms underlying the toxicological effects of PQ in the liver.…”

Host–Guest Formulation of Carboxylatopillar[6]arene with Ergothioneine as a New Antidote for Combinational Detoxification of Paraquat

“…Paraquat (PQ), a quaternary nitrogen herbicide, is highly toxic to human beings and animals. − Accidental or spontaneous ingestion of PQ would cause an acute poisoning reaction that damages the major organs, resulting in rapid multiorgan failure with a mortality rate of 50–80%. − PQ induces its toxic effects mainly through generation of abundant reactive oxygen species (ROS), including H 2 O 2 , • O 2 – , and HO • by redox cycling. − Abundant ROS will destroy mitochondria, resulting in the activity decrease of a variety of antioxidant enzymes and then causing acute alveolitis, inflammatory cell infiltration, rapid pulmonary interstitial fibrosis, and even death. − In clinical practice, several strategies have been developed to detoxify PQ poisoning. Activated carbon and montmorillonite powder are ordinarily used via gastric administration, and 20% mannitol is used as a cathartic for accelerating PQ excretion to prevent its further absorption. − Numerous antioxidants have also been developed to treat PQ poisoning, including vitamin E, vitamin C, and glutathione. − Additionally, hemoperfusion, immunosuppression, and supportive care measures are taken to detoxify PQ poisoning in clinics. ,− Unfortunately, the current treatments are moderately effective and nonspecific, resulting in poor therapeutic outcomes. ,,− …”