Codeine-induced hepatic injury is via oxido-inflammatory damage and caspase-3-mediated apoptosis

2021

Heliyon

Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling

Ajayi

2021

Heliyon

“…Colorimetric methods were employed to assay the cardiac and plasma concentrations of malondialdehyde (MDA) [ 33 , 38 ], reduced glutathione (GSH) [ 39 ], nitric oxide (NO) [ 33 , 39 ], and activities of superoxide dismutase (SOD) [ 40 , 41 ], catalase [ 42 ], glutathione peroxidase (GPx) [ 33 , 37 ], glutathione-S-transferase (GST) [ 33 , 38 ], and myeloperoxidase (MPO) [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

Co-administration of HAART and antikoch triggers cardiometabolic dysfunction through an oxidative stress-mediated pathway

Hamed²

2021

Lipids Health Dis

Background Antikoch and highly active anti-retroviral therapy are effective drugs in the management of tuberculosis and Human Immunodeficiency Virus, respectively. However, these cocktails have been independently associated with the aetiopathogenesis of metabolic syndrome. This study investigated whether or not the co-administration of antikoch and anti-retroviral, as seen in tuberculosis/Human Immunodeficiency Virus co-infection, will produce a similar effect. Also, it evaluated the role of glutathione and adenine deaminase/xanthine oxidase/uric acid signaling in antikoch/anti-retroviral-induced cardiometabolic dysfunction. Methods Male rats of Wistar strain were randomized into four groups: the control, which had 0.5 mL of distilled water as a vehicle, anti-Koch-treated rats that were administered a cocktail of anti-Koch, HAART-treated rats that had a combination of anti-retroviral drugs, and anti-Koch + HAART-treated rats that had treatments as anti-Koch-treated and HAART-treated rats. The treatment was once daily and lasted for eight weeks. One way-analysis of variance followed by Tukey’s posthoc test was used to test for significance and pairwise comparisons respectively. Results Although no changes in body weight gain and cardiac weight were noted, it was found that antikoch and/or HAART caused insulin resistance and elevated blood glucose level. In addition, antikoch and/or HAART led to dyslipidaemia, increased atherogenic indices, and elevated cardiac injury markers. These were accompanied by increased plasma and cardiac concentrations of malondialdehyde and nitric oxide, C-reactive protein, and myeloperoxidase activity, as well as suppressed activities of glutathione peroxidase and glutathione-S-transferase, and a fall in reduced glutathione level. The observed alterations were more pronounced in animals that received a combination of antikoch and HAART. Conclusions This study provides the first evidence that antikoch and/or HAART induce cardiometabolic dysfunction via glutathione suppression and up-regulation of adenine deaminase/xanthine oxidase/uric acid-dependent oxidative stress and inflammatory response. These events were associated with dyslipidaemia and increased atherogenic indices. This infers that regular monitoring of glucose level, insulin sensitivity, lipid profile, and oxido-inflammatory markers is important in patients on antikoch and/or HAART for prompt diagnosis and management of cardiometabolic disorder if it ensues.

“…Although its therapeutic use as an analgesic and antitussive is uncontroversial, the development of tolerance within a short period of use results to its abuse and addiction [7]. It is toxic to cardiorenal tissue [8], liver [9], and neuronal cells [10][11][12]. Codeine has also been found to impair male reproductive function through suppression of circulatory androgen [13] and oxidative testicular and sperm damage [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

In vitro effect of codeine on human sperm motility and DNA integrity

Hamed²,

Ajayi

et al. 2021

Preprint

Purpose This study assessed the in vitro effect of codeine, a popular drug of abuse, on human spermatozoa motility, plasma membrane integrity, DNA integrity, and oxidative stress. Materials and Methods Semen samples were collected from fifteen healthy donors and conventional semen analysis was carried out per the guideline of the World Health Organization. Direct Swim-up technique was performed to obtain highly motile sperm. Samples were incubated at 34.5°C with different concentrations (0, 0.1, 1, 5 and 10 mM) of codeine. The non-exposed (0 mM) was used as the control group. Sperm motility and DNA integrity were assessed at 30, 60, and 90 minutes, while sperm membrane integrity and sperm 8-OHdG level were determined at 90 minutes. Results Codeine at any tested concentration significantly reduced sperm motility and plasma membrane integrity but increased sperm 8-OHdG level compared to the control in a time-dependent manner. Furthermore, codeine at 1, 5, and 10 mM markedly increased sperm DNA damage. In addition, correlation study showed that sperm 8OHdG level was negatively associated with sperm motility, plasma membrane integrity, and DNA integrity. Conclusions Codeine may impair human spermatozoa fertilization capacity by inducing sperm dysmotility and damage to the sperm plasma membrane and DNA through an oxidative stress-dependent mechanism.