Effect of Methoxychlor on Ca²⁺ Movement and Viability in MDCK Renal Tubular Cells

Abstract

The effect of the insecticide methoxychlor on the physiology of renal tubular cells is unknown. This study aimed to explore the effect of methoxychlor on cytosolic Ca 2+ concentrations ([Ca 2+ ] i ) in MDCK renal tubular cells using the Ca 2+ -sensitive fluorescent dye fura-2. Methoxychlor at 5-20 lM increased [Ca 2+ ] i in a concentration-dependent manner. ] i rise by inducing phospholipase C-dependent Ca 2+ release from multiple stores and Ca 2+ entry via protein kinase C-and econazole-sensitive channels. Methoxychlor slightly enhanced or inhibited cell viability in a concentration-dependent, Ca 2+ -independent manner. Methoxychlor induced cell death that may involve apoptosis via mitochondrial pathways.Evidence shows that the pesticide methoxychlor produces harmful effects on the reproductive organs in diverse species [1,2]. Methoxychlor is shown to alter dehydrogenases' activities in human and rat testes [3] and to cause apoptosis via mitochondria-and FasL-mediated pathways in adult rat testis [4]. Methoxychlor inhibits growth of antral follicles by altering cell cycle regulators [5] and causes epigenetic changes in adult ovarian genes [6]. The cellular mechanisms of methoxychlor's effect are explored, and it is shown that methoxychlor induces mitochondrial dysfunction and oxidative stress DNA damage in the mouse ovarian surface epithelium [7,8]

Testimony for veterinary apitherapy

“…87 MXC hepto-toxicity results in significant reduction in total serum protein rather than marked elevation in hepatic marker enzymes(ALT, AST & ALP) 76 as well as changes in inter and intra cellular signaling. 88 Histopathologically, there is changes in hepatocytes 76,89 owing to induction changes in mRNA abundance of genes in the liver and testes, 90 where alterations involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors. 88 MXC affect kidneys causing toxic nephrosis 76…”

Effect of Methoxychlor on Ca^(2+) Homeostasis and Apoptosis in HA59T Human Hepatoma Cells

“…Methoxychlor was shown to induce apoptosis in different cells such as mouse thymocytes (13), rat testis cells (37), immunocytes (14), human oral cancer cells (35) and canine renal tubular cells (5). However, methoxychlor was shown to enhance growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway (21).…”