RESEARCH ARTICLE Effect of vitamin A and vitamin C on attenuation of ivermectin-induced toxicity in male Wistar rats Fatemeh Sadat Hosseini Omshi 1 & Roghayeh Abbasalipourkabir 2 & Maliheh Abbasalipourkabir 1 & Sedigheh Nabyan 1 & Alireza Bashiri 1 & Abolfazl Ghafourikhosroshahi 3 Received: 26 November 2017 /Accepted: 14 August 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract An in vivo study was performed to assay the effects of ivermectin on adult male Wistar rats. Twenty-five male Wistar rats aged 6 to 8 weeks and weighing 150–250 g were divided into five groups of five animals each for the purpose of this study. The groups received ivermectin; a mixture of ivermectin and vitamin A; a mixture of ivermectin and vitamin C; and a mixture of ivermectin, vitamin A, and vitamin C, respectively. One group served as the control group and was treated with double-distilled water. The treatment was carried out once a week for 3 weeks. The results of the study revealed that the animals were less affected as detected by slight changes in the body weight, stress oxidative parameters, serum levels of liver enzymes, kidney function indexes, cell blood counts, and sperm analysis upon exposure to ivermectin. Nevertheless, the use of vitamins A and C might have a promising effect against oxidant-antioxidant imbalance. Although, the administration of free ivermectin has fewer reactions on mammals, use of the drug supplemented with antioxidants such as vitamins A and C moderates its effects. Keywords Ivermectin . Rat . Vitamin A . Vitamin C Introduction Nowadays, a wide range of external and internal parasites has been reported. Parasitic infections have affected more than 200 million people in the world. A chronic parasitic involvement may lead to inflammation and infection, can- cer, and eventually death. Parasitic worm infections and protozoa are the major causes of disease and death world- wide (Idowu et al. 2015 ). Ivermectin (a member of avermectin family) is an anti-insect and anti-parasitic drug with a broad spectrum of activity and high efficacy on internal and external parasites. In veterinary medicine, the use of ivermectin is widespread due to the safety aspects of the drug (Aniagolu et al. 2012). Ivermectin as treatment for internal and external parasites has been used on various types of native animals, wildlife, species of birds, and ex- otic pets such as hedgehogs, snakes, and other reptiles (Plumb 2008). There are glutamate-activated chloride channels with high affinity to ivermectin in nerve and mus- cle cells of invertebrate. Increasing permeability of the cell membrane and hyperpolarization of nerve and muscle cell occur upon binding of ivermectin to the channels (Ikeda 2003). The effects of ivermectin on inhibitory neural inter- faces and its involvement in the lack of ability of muscle contractions, paralysis, and finally death were reported (Ikeda 2003). Ivermectin is highly absorbable and does not influence the cerebrospinal fluid easily; therefore, its toxicity can be limited. Ivermectin can enter the body via the gastrointestinal system and may reach the blood or organs such as the liver and kidney for metabolism (Plumb 2008). Although ivermectin has been introduced as a safe and harmless medication for mammals (Atakisi et al. 2009), considering that it is a xenobiotic for the body, it probably has some effects on the oxidative stress system of the mammalian. Since xenobiotic is alien to the organ- ism, it is expected to cause adverse effects such as toxicity, allergic response, and cancer (Dibyajyoti 2014). Some Responsible editor: Philippe Garrigues * Roghayeh Abbasalipourkabir rpourkabir@hotmail.com; abbasalipourkabir@umsha.ac.ir 1 School of Veterinary Medicine, University of Tehran, Tehran, Iran 2 School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran 3 School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran Environmental Science and Pollution Research https://doi.org/10.1007/s11356-018-2961-7