The present study aimed to investigate whether Lycium barbarum polysaccharides (LBP) would protect against doxorubicin (DOX)-induced testicular toxicity. Male Sprague-Dawley rats were treated with distilled water (4 mL/kg) or LBP (200 mg/kg, p.o.) daily for 10 days and followed by saline (0.9 %, 10 mL/kg) or DOX (10 mg/kg) intravenous injection at day 7. Pretreatment with LBP ameliorated DOX-induced reduction in the testicular weights, sperm concentrations and percentage of motile sperms, as well as the increase in abnormal sperm rate. LBP administration to DOX-treated rats successfully reversed the changes in MDA and GHS-Px levels. Compared with the control, pretreatment with LBP significantly increased the plasma testosterone level in the LBP + DOX group. The histopathology examinations further confirmed that LBP effectively attenuated DOX-induced severe degenerative changes of seminiferous tubules. This study illustrated the capability of LBP in attenuating testicular oxidative stress and protecting testis-specific toxicity in DOX-exposed rats.
Doxorubicin (DOX), a quinone-containing anthracycline antineoplastic, is used for the treatment of solid and hematopoietic tumors. However, its dose-dependent cardiotoxicity hampered its clinical application.1) Recent studies have suggested that DOX-induced cardiotoxicity involves the formation of reactive oxygen species (ROS) and amplification of mitochondrial dysfunction.1,2) Moreover, the anticancer effects of DOX do not follow the identical mechanisms of ROS. The majority of strategies to protect cardiomyocytes against DOX-induced oxidative injury in heart therefore focused on administering antioxidants in the past. 1)A number of antioxidants, such as lycopene, N-acetylcysteine and vitamin E were proved to ameliorate the DOXinduced cardiac cell damage without compromising its antitumor efficacy in the rats or mice model. [3][4][5] However, most of them were tried with limited success in preventing DOX-associated cardiotoxicity in large-sized animals such as dogs or pigs. 6)Lycium barbarum, a famous Chinese medicinal herb, has a long history of use as an antioxidant and to promote sexual fertility. Lycium barbarum polysaccharides (LBP), consisting of various botanic polysaccharide including arabinose, rhamnose, xylose, mannose, galactose and glucose, are the most important functional constituents in red-colored fruits Lycium barbarum. LBP and edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, a potent free radical scavenger, EDA) were found to elicit a typical cardioprotective effect against DOXrelated oxidative stress in rats. 7,8) However, no similar cardioprotective effect of either LBP or EDA was reported in beagle dogs. Electrocardiography (ECG) is one of the standard methods used to assess cardiac function and is often performed to evaluate whether cardioprotective agents would improve DOX-induced conduction abnormalities.9,10) Moreover, the usefulness of biochemical indicators such as serum creatine kinase (CK) and aspartate aminotransferase (AST) in assessment of DOX-associated cardiotoxicity in experimental animals has also been indicated by various studies. 11)The present study aims to explore electrocardiographic and biochemical evidence for the cardioprotective effect of those two antioxidants in DOX-induced acute cardiotoxicity in beagle dogs. MATERIALS AND METHODSChemicals DOX was obtained from Pfizer Italia S.r.l. (Nerviano, Italy) as a 10 mg/bottle lyophilized powder. It was dissolved in 20 ml of 0.9% saline for injection. Lycium Chinese mill Polysaccharide was purchased from Zhejiang Doxorubicin (DOX) is a potent antitumor agent, but the cardiotoxicity mediated by the formation of reactive oxygen species limit its clinical use. The present study aims to explore electrocardiographic and biochemical evidence for the cardioprotective effect of two antioxidants, Lycium barbarum polysaccharides (LBP, the main antioxidant in Lycium barbarum) and edaravone (a potent free radical scavenger, EDA) against DOX-induced acute cardiotoxicity in beagle dogs. In this study, male beagle dogs received daily treat...
1 Hz, were applied. The temperature was ramped from 0 C to 120 C, at a rate of 2 C min ±1 . Films were dried in a vacuum dessicator for at least a week before use, and dry nitrogen flowed through the DMTA oven to prevent water uptake.
Testicular dysfunction is one of the serious secondary complications in diabetes. Lycium barbarum polysaccharide (LBP) has long been considered to possess a wide range of beneficial properties including antiaging, anticancer and reproductive-enhancing. Abnormal autophagy was reported to play a significant role in accelerating diabetic reproductive injury. However, the autophagy regulation mechanism of LBP on diabetic testicular dysfunction is incompletely understood. We investigate the protective effects of LBP on diabetic testicular dysfunction and its underlying mechanism with different approaches. Protective effects of LBP (40 mg/kg) on testicular functions were assessed through the use of sperm parameters, testosterone levels and hematoxylin and eosin staining. Antioxidant capacity and serum malondialdehyde levels were determined using assay kits. Immune intensity of Beclin-1 and LC3I in testes was detected by immunofluorescence staining. Western blot analysis was used to detect expressions of p-PI3K, Akt, p-Akt, Beclin-1, LC3I and LC3II proteins. Q-PCR was used to evaluate Beclin-1 and LC3I mRNA expressions in testis. Administration of LBP (40 mg/kg) considerably recovered testicular function, obviously improved testicular histopathologic structure and significantly increased antioxidant enzyme activities. Immunofluorescence staining showed that immune intensity of Beclin-1 and LC3I significantly decreased in the LBP 40 mg/kg group. The results of Q-PCR and western blot analysis showed that LBP 40 mg/kg significantly downregulated Beclin-1 and LC3I protein expressions upregulated p-PI3K and p-Akt protein expressions and decreased Beclin-1 and LC3I mRNA expressions compared with diabetic mice. In conclusion, inhibition of PI3K/Akt pathway-mediated testicular excessive autophagy may be a target for protective effects of LBP on diabetic testicular dysfunction.
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