Impairment of peripheral neurons by anti-cancer agents, including taxanes and platinum derivatives, has been considered to be a major cause of chemotherapy-induced peripheral neuropathy (CIPN), however, the precise underlying mechanisms are not fully understood. Here, we examined the direct effects of anti-cancer agents on Schwann cells. Exposure of primary cultured rat Schwann cells to paclitaxel (0.01 μM), cisplatin (1 μM), or oxaliplatin (3 μM) for 48 h induced cytotoxicity and reduced myelin basic protein expression at concentrations lower than those required to induce neurotoxicity in cultured rat dorsal root ganglion (DRG) neurons. Similarly, these anti-cancer drugs disrupted myelin formation in Schwann cell/DRG neuron co-cultures without affecting nerve axons. Cisplatin and oxaliplatin, but not paclitaxel, caused mitochondrial dysfunction in cultured Schwann cells. By contrast, paclitaxel led to dedifferentiation of Schwann cells into an immature state, characterized by increased expression of p75 and galectin-3. Consistent with in vitro findings, repeated injection of paclitaxel increased expression of p75 and galectin-3 in Schwann cells within the mouse sciatic nerve. These results suggest that taxanes and platinum derivatives impair Schwan cells by inducing dedifferentiation and mitochondrial dysfunction, respectively, which may be important in the development of CIPN in conjunction with their direct impairment in peripheral neurons.
Background: Chronic exposure to petroleum products’ ingredients, such as basic chemicals, additives, and pollutants, can affect the hematological system and liver. Automobile repair shop mechanics are a group of people who are constantly exposed to petroleum products. In Afghanistan, children labor alongside adults in automobile repair shops. Therefore, we aimed to find the effect of these products on the hematological system and liver function of children and adults at automobile repair shops in Kabul city of Afghanistan. Methods: In this cross-sectional study, individuals who worked in automobile-repair shops in Kabul, Afghanistan, were compared to healthy control groups in two age categories: adults (≥18 years old), and children (<18 years old). Hematological tests for blood indices and biochemical studies for liver function were done. Based on the normal or abnormal distribution of data, the central tendencies of exposed and control groups were compared using the Student's t-test and Mann-Whitney U test respectively. Results: Only MCV was significantly different between adults exposed and control groups in terms of blood indices. MCH, MCV, MID, MPV, PLC, PDW, and Neut/Lym ratios differed significantly between exposed and control groups in children. Albumin and globulin levels in adults, and albumin and AST levels in children were significantly different between the exposed and control groups in terms of liver function tests. Conclusion: Children are more affected by occupational exposure to petroleum products than adults.
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