Pathological and immunohistochemical changes in the liver of monocrotaline-treated rats (original) (raw)

2022, Turkish Journal of Veterinary & Animal Sciences

Introduction Pyrrolizidine alkaloids (PAs) are widely distributed herbal toxins in nature [1-3]. There are about 660 PAs with different structure determined in 6000 plant species of 13 plant families [4-8]. Roughly, 3.0% of the world's flowering plants contain the PAs [2,9-12]. The liver is the primary target organ in PA toxication [2,13]. Pyrrolic metabolites constitute the alkylating reaction with the structural elements of tissues [14]. They form covalent bonds with cellular structures such as DNA, protein, amino acid, and glutathione [2,9,13]. Besides the hepatotoxic effects, PAs have carcinogenetic [11,15-17], antimitotic, and immunosuppressive effects [18]. The antimitotic effects are attributed to binding of the pyrrolic metabolites to proteins or nucleic acids [3,11]. Pyrroles cause degeneration and necrosis in cells through binding proteins of cytoplasm and the thiol groups of nucleic acids [9,11]. Due to attachment of the metabolites to the specific target regions on DNA, G2 and M phases of mitosis do not occur; however, G1 and S phases are not affected. Hepatocytes return to G1 phase again, neglecting G2 or M, and protein synthesis continues in the cell [2]. As a result of antimitotic effects, megalocytic hepatocytes are formed in chronic toxication [1,19-21]. Mutagenic and teratogenic effects also occur when the pyrollic metabolites bind to the DNA helix [13,22]. The carcinogenic effect of PAs is caused by damage of the P53 gene in the DNA [22]. Monocrotaline is a pyrrolizidine alkaloid plant toxin that causes hepatotoxic, pneumotoxic, genotoxic, and nephrotoxic effects in human and animals [5,6,8,10,23]. Although there are many studies on pneumotoxic and genotoxic effects of monocrotaline, its time course and dose-related hepatotoxic effects have been examined in a limited number of studies [6]. This study was performed to investigate the time course and dose-related pathological findings induced by monocrotaline in Wistar rat liver. 2. Materials and methods 2.1. Animals The present study was approved by the Ethics Commission of Fırat University in the convention on 05.02.2014 with the decision number 38.