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Molecular mechanism behind methamphetamine-induced damages in testicular tissue: Evidences for oxidative stress, autophagy, and apoptosis.

Tahmineh PeirouviMazdak Razi
Published in: Andrologia (2022)
Methamphetamine (METH) is shown to cause massive oxidative stress and apoptosis in testicular tissue. This study attempted to investigate the possible effects of METH chronic administration on the crosstalk between oxidative DNA damage (ODD), the ODD repairing process, autophagy, and apoptosis in testicular tissue. For this purpose, 20 rats were divided into control and METH (2.5 mg/kg)-received groups (N = 10 rats/group). Following 7 days, the tubular differentiation (TDI) and spermiogenesis (SPI) indices, histomorphometric alterations, intracytoplasmic carbohydrate and lipid storage in germ and Sertoli cells along with expression levels of proliferating cell nuclear antigen (PCNA), as a key element in regulating base excision repair (BER) enzymes expression/activity were assessed. Moreover, the expression levels of uracil-DNA (UDG) and methylpurine (MPG) DNA glycosylases and microtubule-associated protein light chain 3 (LC3-I/II), and apoptotic cells distribution in testicular tissue were evaluated. Observations revealed that METH significantly suppressed spermatogenesis and spermiogenesis development, altered intracytoplasmic carbohydrate and lipid storage, increased ODD, and suppressed the PCNA expression compared to the control group (p < 0.05). Furthermore, METH-received animals exhibited a remarkable (p < 0.05) reduction in UDG and MPG, increment in LC3-I/II expressions, and apoptotic cells distribution. In conclusion, METH consumption results in a failed intracytoplasmic glucose storage (primary metabolites of Sertoli and germ cells) and oxidative stress (OS) circumstance in the testicular tissue. Further, METH can induce ODD by suppressing the expression levels of PCNA and BER enzymes, UDG and MPG. Finally, we demonstrated that METH-induced massive ODD is capable of initiating autophagy signalling that leads to progressive apoptosis in the testicular tissue.
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