Arsenic effect was studied at two dosage levels (0.5 mg and 1 mg/kg) for 45 days in two regions of brain, viz., cerebral hemisphere (CH) and cerebellum (C) in adult mice. This study included the antioxidant profile namely superoxide dismutase (SOD), catalase, lipid peroxidation, reduced glutathione, ascorbic acid and total sulphydryl groups. Adenosine triphosphatase (ATPase), succinic dehydrogenase (SDH), phosphorylase together with glycogen and protein levels were also estimated as metabolic indices in the brain regions of mice. A notable decrease was detected in the activities of the enzymes and in the levels of other metabolites together with a significant increase in the lipid peroxidation, glycogen and inorganic arsenic levels after arsenic administration. Supplementation of vitamin A to the arsenic treated mice brought about no significant variation in these antioxidant and metabolic indices in comparison to that of control, revealing amelioration by vitamin A on arsenic exerted metabolic and neurotoxic effects in mice.Key words ---arsenic, vitamin A, antioxidant system, metabolic and neurotoxic effect in part by inducing rapid burst of reactive oxygen species (ROS) in mammalian cells, resulting in oxidative stress 12,13) and carcinogenesis in man. 14) Studies document that arsenic generates ROS such as hydrogen peroxide, superoxide (O 2•-), hydroxyl (OH • ) and peroxyl (ROO • ) radicals. 13) These free radicals and the other reactive species are constantly produced in the brain in vivo.15) Experiments on human fetal brain explants on exposure to arsenic in culture have showed disturbances in lipid peroxidation, generation of ROS and apoptosis. 16) Adenosine triphosphatase (ATPase) and succinic dehydrogenase (SDH) (enzymes of the inner mitochondrial membrane) are concerned with respiration, and energy generation; hence, are essential for cell survival. Respiratory chain is the major source of ROS, hence mitochondrial oxidative damage is thought to be a proximal cause of metabolic effects. 17,18) Metabolism in fish brain was also affected by arsenic poisoning 19) in addition to other pathological effects in general metabolism of animal tissues. 20)

Tumor growth and proliferation are regulated by numerous mechanisms. Communication between intracellular organelles has recently been shown to regulate cellular proliferation and fitness. The way lysosomes and mitochondria communicate with each other (lysosomal/mitochondrial interaction) is emerging as a major determinant of tumor proliferation and growth. About 30% of squamous carcinomas (including squamous cell carcinoma of the head and neck, SCCHN) overexpress TMEM16A, a calcium-activated chloride channel, which promotes cellular growth and negatively correlates with patient survival. TMEM16A has recently been shown to drive lysosomal biogenesis, but its impact on mitochondrial function is unclear. Here, we show that (1) patients with high TMEM16A SCCHN display increased mitochondrial content specifically complex I; (2) In vitro and in vivo models uniquely depend on mitochondrial complex I activity for growth and survival; (3) β-catenin/NRF2 signaling is a critical linchpin that drives mitochondrial biogenesis, and (4) mitochondrial complex I and lysosomal function are codependent for proliferation. Taken together, our data demonstrate that LMI drives tumor proliferation and facilitates a functional interaction between lysosomes and mitochondria. Therefore, inhibition of LMI may serve as a therapeutic strategy for patients with SCCHN.