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

Abstract

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.

miRNA-210 increased apoptosis of testicular tissues in cryptorchidism mice model through INHBB-Smad2/3 signaling pathway

“…Apoptosis, a common process in normal spermatogenesis in mammals, supported cell homeostasis and a good balance between mature germinating and supporting cells. However, the apoptotic process of testicular germ cells can be enhanced by a variety of physical and chemical stresses, such as trauma, heat, radiation, or withdrawal of hormonal support [3,30]. The signi cant decrease in testicular weight and diameter observed in the cryptorchidism group seemed to be mainly related to extensive germ cell loss parallel to the reduction of testicular uid produced by Sertoli cells [31].…”

DNA damage in testicular germ cells and spermatozoa. When and how is it induced? How should we measure it? What does it mean?

“…Oxidative stress and apoptosis are therefore closely intertwined in the induction of testicular DNA damage; apoptosis inducing a significant increase in the intracellular generation of ROS while oxidative stress can also activate the intrinsic apoptotic cascade. As a result, both oxidative DNA damage and apoptosis‐related, nuclease‐induced DNA fragmentation are observed when the testes is under stress, whether this is chemically, 36–38 psychologically, 39 or surgically 40 induced or the result of exposures to excessive ionizing radiation 41 or heat 42 . Several studies indicate that the germ‐line DNA damage associated with such testicular stress may be alleviated with reagents designed to impede the oxidative damage process such as lactoferrin 36 mitochondrial permeability transition pore inhibitors, 40 curcumin, 43 dimethyl sulfoxide, 41 lutein, 44 vitamin C, 45 vitamin E and vitamin C in combination, 46 silymarin, 47 trigonelline, 42 melatonin, 42 p‐tyrosol, 48 beta‐caryophyllene, 49 saponin 38 and a variety of other antioxidant compounds, administered alone or in combination 50–52 .…”

Neuroprotective activity of green synthesized silver nanoparticles against methamphetamine-induced cell death in human neuroblastoma SH-SY5Y cells

“…The accumulation of evidence suggests that Meth also causes oxidative stress by causing an imbalance between the production of reactive oxygen species (ROS) and the ability of antioxidant enzymes to scavenge them. Overproduction of ROS can damage mitochondrial and nuclear DNA, lipids, and proteins in cells 9 , 10 .…”