Vitamin D attenuates nucleoside reverse transcriptase inhibitor induced human skeletal muscle mitochondria DNA depletion

Abstract

Objective To evaluate the impact of the active metabolite of vitamin D, 1α,25-dihydroxycholecalciferol (1,25D3), on nucleoside reverse transcriptase inhibitor (NRTI) induced mitochondrial DNA (mtDNA) depletion in human skeletal muscle myoblasts and myotubes. Design mtDNA was quantified in human skeletal muscle myoblasts and myotubes following 1,25D3 and NRTI treatment using real-time PCR. Methods Human skeletal muscle myoblasts and myotubes were treated with didanosine (ddI), stavudine (d4T), zidovudine (ZDV), lamivudine (3TC) and abacavir (ABC) alone or in combination either in the presence or absence of 1,25D3 for 5 days. Cells were harvested, DNA extracted and mtDNA quantified. Results ddI and ddI-d4T significantly decreased both myoblast and myotube mtDNA in the absence of 1,25D3 compared with untreated controls (P ≤ 0.029). In addition, the ZDV-3TC combination resulted in a 47% decrease in myotube mtDNA (P = 0.005). 1,25D3 increased myotube mtDNA levels in ddI, ZDV, 3TC, ABC, ddI-d4T, d4T-3TC, ZDV-3TC, ZDV-ABC and ZDV-3TC-ABC-containing regimens and myoblast mtDNA levels in ddI, d4T, ZDV, 3TC, ddI-d4T, ZDV-3TC and ZDV-ABC-containing regimens. Of note, 1,25D3 protected against myotube mtDNA depletion following ZDV-3TC treatment, rendering them similar to 1,25D3 untreated controls (P = 0.62), and increased both myotube and myoblast mtDNA two to three-fold in ddI-containing regimens (P < 0.05). Conclusion 1,25D3 confers a protective effect against NRTI-induced mitochondrial toxicity in skeletal muscle myoblasts and myotubes. These findings support a protective role for vitamin D in preventing mitochondrial toxicity and suggest that supplemental vitamin D may protect against NRTI-associated mitochondrial toxicity.

Oxidative Stress and BPA Toxicity: An Antioxidant Approach for Male and Female Reproductive Dysfunction

“…Quan et al [99] demonstrated that oral BPA exposure in dams (gestational days (GD)) [14][15][16][17][18][19][20][21] provokes an increased ROS production, the activation of the apoptotic pathway in the testis of male offspring, confirmed by histopathological changes. BPA exposure in CD-1 dams (GD 7-14) also led to the alteration of sperm quality and motility in adult male mice, with changes in oxidative balance [100]. Furthermore, in a murine model of chronic BPA exposure of dams, during all gestational period, and continuing the oral administration to male pups until to sexual maturation, damaged spermatogenesis was observed in progenies [101].…”

Biomechanical Process of Skeletal Muscle under Training Condition Based on 3D Visualization Technology

“…The third method is to use a ranging sensor to describe the motion by distance. The extraction of data on bone and the joint center has become a research hotspot [ 10 ]. The extraction of human bones and joint centers based on point cloud data is processed by processing the point cloud data of the real human body acquired by the three-dimensional scanner, thereby extracting semantic information such as the skeleton and joint center of the human body model [ 11 – 13 ].…”

PPD-induced monocyte mitochondrial damage is associated with a protective effect to develop tuberculosis in BCG vaccinated individuals: A cohort study

“…However, although the exact significance of the cells´ death in the development of the disease is still uncertain, the manipulation of cell death pathways will eventually affect the course of the infection [ 11 , 15 ]. Although the interplay between the mononuclear phagocytes-apoptosis and the mycobacterial control is still under investigation, there is evidence that apoptosis pathways are able to trigger inflammatory mediators (pyroptosis) and autophagy which may serve to limit bacterial intracellular growth [ 16 – 19 ].…”