aboalghasem taghavi holagh

Doxorubicin (DOX) is an effective drug in the treatment of various cancers whose usage has been limited due to the cardiac toxicity. The present study aimed to investigate the combination effect of troxerutin (TRX; It is derived from the flavonoid rutin and has pharmacological properties) and high-intensity interval training (HIIT) on DOX-induced cardiotoxicity and expression of mitophagy genes Mfn2 and Parkin in rat cardiac cells.

Male Wistar rats were randomly divided into five groups (n = 10): 1) Control, 2) DOX, 3) HIIT + DOX, 4) TRX + DOX, and 5) HIIT + TRX + DOX. After the last session of HIIT, the trained and time-matched control rats were injected with DOX (20 mg/kg, ip). To confirm the induction of doxorubicin cardiotoxicity, it was shown that DOX injection increased serum level of lactate dehydogenase from 57±3 U/l to 171±6 U/l. The expression of mitophagy genes including Mfn2 and Parkin was measured by Real-Time PCR.

DOX injection decreased the expression of mitophagy genes Mfn2 and Parkin (P<0.01). The combined effect of HIIT exercise and troxerutine consumption led to a significant increase in the expression of mitophagy genes Mfn2 (P<0.05) and Parkin (P<0.01) compared to the DOX group.

The combined application of HIIT exercise and troxerutin can increase the expression of mitophagy genes Mfn2 and Parkin in cardiac cells of DOX-receiving rats and reduce DOX-induced cardiac toxicity.

Cancers represent an important cause of morbidity and mortality, cause more than 12% of deaths in the world. Doxorubicin (DOX) is an effective drug in the treatment of various cancers whose usage has been limited due to cardiac toxicity. Troxerutin (TRX) is derived from rutin flavonoids and has multiplex pharmacological properties. The present study aimed to investigate the combined effect of troxerutin and high-intensity interval training (HIIT) on DOX-induced cardiac toxicity and the expression of antioxidant genes in rat hearts.

Male Wistar rats were randomly divided into five groups (n = 10): 1) Control, 2) DOX, 3) HIIT + DOX, 4) TRX + DOX, and 5) HIIT + TRX + DOX. After the last session of HIIT, the trained and time-matched control rats were injected with DOX (20 mg/kg, ip). The Creatine kinase (CKMB) and Lactate dehydrogenase (LDH) changes were measured by spectrophotometry and ELISA. Expression of antioxidant genes was measured by Real-Time PCR.

DOX injection increased serum CKMB and LDH in rats in comparison to the control group (p < 0.05) and (P <0.01), respectively. HIIT exercise and troxerutin, alone or in combination, reduced the serum CKMB and LDH levels (p < 0.05) and their combined effect was greater than those of individual treatments (p < 0.01). DOX injection decreased the expression of Nrf2 and Foxo1 antioxidant genes as compared with a control group (P <0.01). HIIT exercise and troxerutin consumption alone increased the expression of the Foxo1 gene as compared with the DOX group (P <0.05) and their combined effect was greater than either alone (P <0.01). HIIT exercise and troxergotTroxerutin consumption alone increased the expression of the Nrf2 gene insignificantly, but their combined effect was significantly increased (P <0.01).

The combined effect of HIIT exercise and troxerutin is a promising strategy to prevent DOX-induced cardiac toxicity and increase the expression of antioxidant genes in rat hearts.

Doxorubicin (DOX) is an effective drug in the treatment of various cancers whose usage has been limited due to the cardiac toxicity. Troxerutin (TRX) is derived from rutin flavonoids and has multiplex pharmacological properties. The aim of the present study was to investigate the combination effect of high-intensity interval training (HIIT) and troxerutin on DOX-induced cardiac toxicity and indices of mitochondrial function in rat hearts.

Male Wistar rats were randomly divided into five groups (n = 10): 1) Control, 2) DOX, 3) HIIT + DOX, 4) TRX + DOX, and 5) HIIT + TRX + DOX. After the last session of HIIT, the trained and time-matched control rats were injected with DOX (20 mg/kg, ip). The Creatine kinase (CKMB) changes was measured by spectrophotometry and ELISA. Mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential were measured by determining the intensity of relevant fluorescent dyes.

DOX injection increased serum CKMB in rats in comparison to control group (P<0.05). HIIT exercise and troxerutin, alone or in combination, reduced the serum CKMB and mitochondrial ROS levels (P<0.05) and their combined effect was greater than those of individual treatments (P<0.01). DOX injection reduced the mitochondrial membrane potential as compared with control group (P<0.01). While the effect of HIIT training or troxerutin alone were not significant on the mitochondrial membrane potential, their combined application significantly increased the mitochondrial membrane potential compared with DOX group (P<0.05).

The combined effect of HIIT exercise and troxerutin is a promising strategy to prevent the DOX-induced cardiac toxicity and improve mitochondrial function in rat heart.

Previous researchs has shown that exercise and antioxidants consumption have positive effect on oxidative stress. Therefore, this study was carried out aiming at investigating the effects of 12 weeks of exercise on a running wheel, with and without consumption of the extratct of Eriobotrya japonica flowers, on MANF level in the cerebellum of rats subjected to 6-hydroxydopamine (6-OHDA). Rats were divided into 6 groups: Base, control-treatment, training-healthy, training-treatment, extract-treatment, and training-extract-treatment. Training groups were housed individually in cages with attached running wheels, and the extracts group received 200 mg/kg bw of the extract, 3 times per week during the research period. The 6-hydroxydopamine solution (250 mg/kg bw) was stereotaxically injected into intracerebroventricular (ICV) region of the brain. MANF levels in the cerebellum were measured by ELISA. Data were analyzed using one-way ANOVA and post-hoc LSD test. In this investigation, the voluntary training on running wheel along with consumption of the extract significantly prevents the decrease in MANF levels in pre-treatment groups, (p=0.031) and (p=0.022). The difference between the control-training group and supplementation group as well as other four groups was statistically significant (all p<0.05). The results of the present study showed that pre-treatment with voluntary training or extract of Eriobotrya japonica flower increases neuroprotection against the stress induced by ICV injection of 6-OHDA.