Evaluation of skeletal muscle function in male rats with doxorubicin-induced myopathy following various exercise techniques: the significant role of glucose transporter 4.

A common anthracycline antibiotic used to treat cancer patients is doxorubicin (DOX). One of the effects of DOX therapy is skeletal muscle fatigue. Our goal in this research was to study the beneficial effect of exercise on DOX-induced damaged muscle fibers and compare the effect of different exercise strategies (prophylactic, post- toxicity and combined) on DOX toxicity. Five groups were created from 40 male rats: group I, control group; group II, DOX was administered intraperitoneally for 2 weeks over 6 equal injections (each 2.5 mg/kg); group III, rats trained for 3 weeks before DOX; group IV, rats trained for 8 weeks after DOX; and group V, rats were trained for 3 weeks before DOX followed by 8 weeks after. Measures of oxidative damage (H2O2, catalase), inflammation (TNF-α), and glucose transporter 4 (GLUT4) expression on skeletal muscle were assessed. Also, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was estimated. Skeletal performance was evaluated by contraction time (CT), half relaxation time (1/2 RT), and force-frequency relationship by the end of this research. The current study demonstrated a detrimental effect of DOX on skeletal performance as evidenced by a significant increase in CT and 1/2 RT compared to control; in addition, H2O2, TNF-α, and HOMA-IR were significantly increased with a significant decrease in GLUT4 expression and catalase activity. Combined exercise therapy showed a remarkable improvement in skeletal muscle performance, compared to DOX, CT, and 1/2 RT which were significantly decreased; H2O2 and TNF-α were significantly decreased unlike catalase antioxidant activity that significantly increased; in addition, skeletal muscle glucose metabolism was significantly improved as GLUT4 expression significantly increased and HOMA-IR was significantly decreased. Exercise therapy showed significant improvement in all measured parameters relative to DOX. However, combined exercise therapy showed the best improvement relative to both pre-exercise and post-exercise groups.

Nanotechnology improves the therapeutic efficacy of gemcitabine against a human hepatocellular carcinoma cell line and minimizes its in vivo side effects.

Nanotechnology has become a promising approach for addressing cancer therapy limitations because it reduces side effects and increases the efficacy of antineoplastic agents. Therefore, this research was designed to compare the in vitro therapeutic efficacy and in vivo adverse effects of gemcitabine (GEM) and gemcitabine-loaded silver nanoparticles (GEM-AgNPs). GEM molecules were successfully attached to AgNP surfaces with a homogenous and spherical shape. The zeta size of AgNPs and GEM-AgNPs was 79.35 ± 3.2 and 75.1 ± 7 nm, respectively. The anticancer effect of AgNPs and GEM-AgNPs was investigated against a human hepatocellular carcinoma cell line (HepG2), and cytotoxic activity was evaluated by MTT assay. Apoptosis/necrosis and cell cycle arrest were also assessed. The cytotoxic activity was recorded in a concentration-dependent way. The findings have shown that GEM-AgNPs induced a better cytotoxic effect with an IC50 value of 13.63 µg/mL compared to GEM (IC50 value of 24.19 µg/mL) or AgNPs alone (IC50 value of 50.6 µg/mL). GEM-AgNPs induced pre-G1 arrest and apoptotic/necrotic cell death. Our in vivo analysis involved the use of 40 male rats assigned equally into the control rats, and rats injected intraperitoneally with GEM (134 mg/kg), AgNPs (1 mg/kg), and GEM-AgNPs (134 mg/kg). GEM and GEM-AgNPs were administered on the 1st, 7th, and 14th day of the experiment. Intraperitoneal GEM injection induced marked hematological, biochemical, hepatorenal, and histopathological alterations, while the loading of GEM in AgNPs to some extent ameliorated these alterations and significantly improved its therapeutic efficacy against HepG2 cells. These findings indicate the potential use of GEM-AgNPs in the clinical setting for anticancer treatment.

Contribution of angiotensin II in hepatic ischemia /reperfusion induced lung injury: Acute versus chronic usage of captopril.

BACKGROUND: Acute lung injury is one of the most popular consequences of hepatic ischemia/reperfusion (I/R) injury. Recently it was documented that renin-angiotensin system plays a key role in tissue inflammation, generation of reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-α) (the principal liver injury mediators) during I/R. MATERIAL AND METHODS: We investigated the effect of acute versus chronic usage of angiotensin converting enzyme inhibitor (captopril) on liver inflammation and lung injury caused by hepatic ischemia for 1h followed by 24h reperfusion. Forty adult Wistar male rats were divided into sham, I/R, I/R-acute captopril (100 mg/kg, 24 and 1.5 h before surgery) and I/R-chronic captopril (10 mg/kg/day for 28 days before surgery) groups. RESULTS: We found captopril pretreatment significantly decreased liver damage indices, adhesion molecules, and TNF-α level in hepatic and tracheal tissues. Histologically, acute captopril pretreatment significantly decreased hepatic Kupffer cells number and lung α-smooth muscle actin expression more than chronic pretreatment. Increased tracheal tone, in response to acetylcholine, was suppressed by acute and chronic captopril pretreatment. CONCLUSION: Angiotensin II plays a key role in tissue inflammation and airway hyperresponsiveness (AHR) via enhancing production of TNF-α. With more protection observed in lung, acute captopril could attenuate liver-induced lung injury via lowering TNF-α; a suggested possible mediator of airway hyperreactivity.

Chlorella vulgaris ameliorates testicular toxicity induced by deltamethrin in male rats via modulating oxidative stress.

This study was carried out to investigate the potential effects of Chlorella vulgaris (CV) on testicular function and oxidant/antioxidant status in normal and deltamethrin-intoxicated rats. Forty adult male rats were drenched either with normal saline, CV (50 mg/kg), deltamethrin (DM) (3 mg/kg), or CV combined with DM, daily for 8 weeks. At the end of the protocol, the epididymal sperm quality was evaluated and the testicular superoxide dismutase (SOD), catalase enzyme (CAT) and malondialdehyde (MDA), and the serum testosterone levels were estimated. Normal rats treated with CV showed a significant increase in the total sperm number/epididymal tail, testicular SOD, and CAT levels with a significant decrease in the testicular MDA. Deltamethrin intoxication significantly decreased the proportions of motile and live sperm, the testosterone concentration, the testicular SOD and CAT levels, whereas it significantly increased the proportion of abnormal sperm and the testicular MDA. Chlorella vulgaris treatment significantly ameliorated the adverse effects of DM-intoxication and restored most of the parameters to levels that are comparable to those of the control group. In conclusion, CV administration improved the testicular function of normal rats and ameliorated the effect of severe oxidative stress conditions.