Effects of tramadol administration on male reproductive toxicity in Wistar rats The role of oxidative stress, mitochondrial dysfunction, apoptosis-related gene expression, and nuclear factor kappa B signalling.

AIM: The present study investigated the role of redox balance, inflammation, mitochondrial dysfunction, and apoptosis in Tramadol (Tra)-induced testicular toxicity. METHOD: Twenty-four male Wistar rats were randomly divided into either the control group or the groups receiving different doses of Tra (25, 50, and 75 mg/kg/day, i.p.) for 21 successive days. Testicular tissues were collected for oxidative stress, mitochondrial function, sperm assays and histopathological evaluation. Real-time polymerase chain reaction was performed to evaluate the markers of inflammation and apoptosis. RESULTS: Tra caused a significant reduction in the sperm count, motility and morphology, while it caused a marked increase in oxidative stress parameters. In addition, Tra induced testicular mitochondrial dysfunction due to the collapse of mitochondrial membrane potential and mitochondrial swelling. It also led to the significant inhibition of anti-apoptotic Bcl-2 expression, besides a significant increase in pro-apoptotic Bax expression. There was a significant increase in the level of tumour necrosis factor-α, interlukin-1ß and nuclear factor kappa B. Histopathological degenerative changes were observed in the testis after Tra exposure. CONCLUSIONS: The present results suggest that Tra exposure may lead to reproductive toxicity due to the loss of the antioxidant defence system, mitochondrial dysfunction, and activation of inflammatory and apoptotic pathways (Tab. 4, Fig. 5, Ref. 63).

Mitochondrial toxicity of aluminium nanoparticles in comparison to its ionic form on isolated rat brain mitochondria.

OBJECTIVES: The aim of this study was to evaluate the toxic effect of AlNPs on rat brain mitochondria and compare it with that of aluminium's ionic form. METHODS: Mitochondria were isolated from rat brain. Isolated mitochondria were treated with normal saline (Control) and different concentrations of aluminium ions (AlIs) and AlNPs (50, 100 and 200 µM). Then, the effect of AlNPs on electron transport chain complexes as well as various endpoints such as mitochondrial oxidative damage (reactive oxygen species, lipid peroxidation, glutathione, and protein carbonyl) and mitochondrial function were assessed. Also, apoptosis was evaluated by cytochrome c release, mitochondrial membrane potential and swelling. RESULTS: When compared to the control group, the exposure to AlNPs showed a marked elevation in oxidative stress markers and inhibition of complex III which was accompanied by disturbance in mitochondrial function. Also, AlNPs induced a significant collapse of mitochondrial membrane potential, mitochondrial swelling, and cytochrome c release. CONCLUSIONS: The comparison of mitochondrial toxicity markers between both forms of aluminium revealed that the toxic effect of AlNPs on isolated brain mitochondria was substantially greater than that that caused by AlIs, which can probably be ascribed to its higher reactivity (Tab. 1, Fig. 8, Ref. 45).

Acrylamide attenuated immune tissues' function via induction of apoptosis and oxidative stress: Protection by l-carnitine.

Acrylamide (ACR), with high prevalence in starchy food, has been associated with the development of several organ toxicities such as immunotoxicity. This study aimed to demonstrate the role of oxidative stress and apoptosis as the mechanisms involved in ACR-induced immunotoxicity in mice. Mice were randomly assigned to six groups and treated as follows: control (normal saline), cyclophosphamide (200 mg kg-1), ACR groups (12.5, 25 and 50mg kg-1, orally), and l-carnitine (l-CAR; 100 mg kg-1) + ACR (50 mg kg-1). After 30 days of exposure, mice were killed and immunotoxic response was evaluated via immune blood cells count and body/organ weights. Oxidative stress parameters and pathological examination were done in thymus and spleen. Also, the apoptosis was evaluated via flow cytometric by annexin V/FITC kit in the splenocytes. Our results indicated that ACR could induce immunotoxicity characterized by reduction in immune blood cells, body/organ weights, and pathological changes in spleen. The assessment of oxidative stress markers revealed increase in lipid peroxidation, protein carbonyl content, and depletion of glutathione level. Also, increased apoptosis was observed in splenocytes after ACR administration compared to the control group. These alterations were markedly normalized by coadministration of l-CAR (as a potent antioxidant). Taken together, the results of this study showed the potential of ACR to induce immunotoxicity through provoking oxidative stress and inducing apoptosis and the protective effect of l-CAR to attenuate this toxicity. These findings will help in elucidating the toxicity mechanism induced by ACR.