Tamoxifen inhibits mitochondrial membrane damage caused by disulfiram.

In this work, we studied the protective effects of tamoxifen (TAM) on disulfiram (Dis)-induced mitochondrial membrane insult. The results indicate that TAM circumvents the inner membrane leakiness manifested as Ca2+ release, mitochondrial swelling, and collapse of the transmembrane electric gradient. Furthermore, it was found that TAM prevents inactivation of the mitochondrial enzyme aconitase and detachment of cytochrome c from the inner membrane. Interestingly, TAM also inhibited Dis-promoted generation of hydrogen peroxide. Given that TAM is an antioxidant molecule, it is plausible that its protection may be due to the inhibition of Dis-induced oxidative stress.

Renoprotective effects of aliskiren on adenine-induced tubulointerstitial nephropathy: possible underlying mechanisms.

The present study investigated the possible renoprotective effect of direct renin inhibitor (aliskiren) on renal dysfunctions, as well as its underlying mechanisms in rat model of adenine-induced tubulointerstitial nephropathy. Forty male Sprague-Dawley rats were randomized into 4 groups; normal group, aliskiren group (normal rats received 10 mg/kg aliskiren), adenine group (animals received high-adenine diet for 4 weeks and saline for 12 weeks), and adenine + aliskiren group (animals received adenine for 4 weeks and aliskiren 10 mg/kg for 12 weeks). It was found that adenine caused significant decrease in body mass, Hb, HR, serum Ca(2+), eNOS and nrf2 expression, GSH, and catalase in kidney tissues with significant increase in arterial blood pressure (ABP), serum creatinine, BUN, plasma renin activity (PRA), K(+) and P, urinary albumin excretion (UAE), caspase-3, and MDA (lipid peroxidation marker) in kidney tissues compared to normal group (p < 0.05). Administration of aliskiren caused significant improvement in all studied parameters compared to adenine group (p < 0.05). We concluded that aliskiren has renoprotective effect against adenine-induced nephropathy. This might be due to inhibition of PRA, attenuation of oxidative stress, activation of Nrf2 and eNOS genes, and suppression of caspase-3.

Effect of oxidative stress on Rho kinase II and smooth muscle contraction in rat stomach.

Recent studies have shown that both Rho kinase signaling and oxidative stress are involved in the pathogenesis of a number of human diseases, such as diabetes mellitus, hypertension, and atherosclerosis. However, very little is known about the effect of oxidative stress on the gastrointestinal (GI) smooth muscle Rho kinase pathway. The aim of the current study was to investigate the effect of oxidative stress on Rho kinase II and muscle contraction in rat stomach. The peroxynitrite donor 3-morpholinosydnonimine (SIN-1), hydrogen peroxide (H2O2), and peroxynitrite were used to induce oxidative stress. Rho kinase II expression and ACh-induced activity were measured in control and oxidant-treated cells via specifically designed enzyme-linked immunosorbent assay (ELISA) and activity assay kits, respectively. Single smooth muscle cell contraction was measured via scanning micrometry in the presence or absence of the Rho kinase blocker, Y-27632 dihydrochloride. All oxidant agents significantly increased ACh-induced Rho kinase II activity without affecting its expression level. Most important, oxidative stress induced by all three agents augmented ACh-stimulated muscle cell contraction, which was significantly inhibited by Y-27632. In conclusion, oxidative stress activates Rho kinase II and enhances contraction in rat gastric muscle, suggesting an important role in GI motility disorders associated with oxidative stress.

Enhancement of renal oxidative stress by injection of angiotensin II into the paraventricular nucleus in renal ischemia-reperfusion injury.

This study was designed to investigate whether microinjection of angiotensin II (Ang II) into the hypothalamic paraventricular nucleus (PVN) in renal ischemia-reperfusion (IR) injury has any effect on renal oxidative stress and damage through renal sympathetic nerve activity (RSNA). One week before the induction of left renal IR injury, right nephrectomy was performed and a cannula was placed into the right PVN. Rats were then distributed among 4 groups (n = 6); Sham, IR, IR + Ang II, and IR + Ang II + losartan. Renal IR injury was induced by clamping the left renal artery for 45 min followed by 24 h reperfusion. Losartan (0.3 µg) and Ang II (3 ng) were microinjected into the PVN at 20 min and 10 min, respectively, before the induction of IR injury. Ang II increased plasma creatinine, urinary NAG activity, and histological changes, and enhanced RSNA compared with the IR group (p < 0.05). Ang II increased malondialdehyde (MDA) levels and reduced superoxide dismutase (SOD) activity in the kidney compared with IR injury. Losartan caused a reduction in plasma creatinine, urinary NAG activity, histological changes, renal sympathetic nerve activity (RSNA), and renal MDA levels, and increased renal SOD activity compared with the IR group (p < 0.05). These data demonstrated that increased RSNA activity, via microinjection of Ang II into the PVN, exaggerated renal IR injury by inducing oxidative stress in the kidney.

Oxidative stress and lung function profiles of male smokers free from COPD compared to those with COPD: a case-control study.

BACKGROUND: The mechanisms of smoking tobacco leading to chronic obstructive pulmonary disease (COPD) are beginning to be understood. However, conclusions about the role of blood or lung oxidative stress markers were disparate. AIMS: To investigate the oxidative stress in blood or lung associated with tobacco smoke and to evaluate its effect on pulmonary function data and its relation with physical activity. METHODS: It is a case-control study. Fifty-four male-smokers of more than five pack-years (PY) and aged 40-60 years were included (29 Non-COPD, 16 COPD). Physical activity score was determined. Blood sample levels of malondialdehyde (MDA), protein-cys-SH (PSH), and Glutathione (GSH) were measured. Fractional exhaled nitric oxide (FeNO) and plethysmographic measurements were performed. Correlation coefficients (r) evaluated the association between oxidative stress markers and independent variables (plethysmographic data and physical activity score). RESULTS: Non-COPD (48 ± 6 years) and COPD (49 ± 5 years) groups had similar tobacco consumption patterns, that is, 27 ± 14 PY versus 30 ± 19 PY, respectively. Compared to the Non-COPD group, the COPD group had significantly lower levels of GSH and PSH, that is, mean ± SE were 40 ± 6 versus 25 ± 5 µg/mL and 54 ± 10 versus 26 ± 5 µg/g of hemoglobin, respectively. However, MDA level and FeNO values were similar. In the COPD group, none of the oxidative stress markers was significantly correlated with plethysmographic data or physical activity score. In the Non-COPD group, GSH was significantly correlated with physical activity score (r = 0.47) and PSH was significantly correlated with total lung capacity (TLC) (r = -0.50), residual volume (r = 0.41), and physical activity score (r = 0.62). FeNO was significantly correlated with TLC of the COPD group (r = -0.48). CONCLUSION: Compared to the Non-COPD group, the COPD group had a marked decrease in blood antioxidant markers (GSH and PSH) but similar blood oxidant (MDA) or lung (FeNO) burden.