Protective effects of Danshen injection against erectile dysfunction via suppression of endoplasmic reticulum stress activation in a streptozotocin-induced diabetic rat model

Abstract

BackgroundErectile dysfunction (ED) is a common complication of diabetes. This study aimed to explore the beneficial effect of Danshen injection on ED in a streptozotocin (STZ)-induced diabetic rat model and the underlying mechanism.MethodsThe diabetic rat model was established by an intraperitoneal injection of 60 mg/kg STZ in male Sprague-Dawley rats. The diabetic rats were intraperitoneally injected with Danshen solution (0.5 or 1 mL/kg/day) or the same volume of saline for 6 weeks. Age-matched rats served as controls. After 6 weeks, erectile function and histological morphology of the corpora cavernosum were assessed. Oxidative stress indicators, including superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and reactive oxygen species (ROS) levels, were measured in penile tissues. The expression levels of glucose-regulated protein 78 (Grp78), growth arrest and DNA damage-inducible gene 153 (GADD153/CHOP) were determined by immunohistochemistry, immunoblotting, and RT-PCR. Apoptosis was detected by a TUNEL assay.ResultsThe erection times of diabetic rats were significantly less than those of control rats. Danshen injection could improve erectile function via increased erection times. Danshen injection was also found to ameliorate the morphological abnormalities of the corpora cavernosum, to reduce the number of apoptotic cells, and to suppress caspase-3 activation in penile tissue, accompanied by downregulation of the endoplasmic reticulum stress biomarkers Grp78 and CHOP. Danshen injection could increase SOD activity as well as reduce ROS and MDA levels in diabetic rats, indicating suppression of oxidative stress.ConclusionDanshen injection could rescue diabetes-associated ED, possibly via suppressing the oxidative stress and endoplasmic reticulum (ER) stress-induced apoptosis pathways.

Metformin protects against diabetes-induced heart injury and dunning prostate cancer model

“…Homocysteine (HCys) level was assayed using ELISA kit according to instructor’s manual. Reactive oxygen species (ROS) levels, total oxidant status (TOS), and total antioxidant status (TAS) in the heart tissues were analyzed according to Zhang et al, 36 Erel, 37,38 respectively. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) activities were assessed by the methods described by Aebi, 39 Mylorie et al, 40 Paglia and Valentine 41 and modified by Wendel, 42 Beutler, 43 and Habig and Jacoby, 44 respectively.…”

Effect of vitamin B6on brain damage in valproic acid induced toxicity

“…Brain tissues were homogenized with cold saline (0.9% NaCl) and then centrifuged. The collected supernatants were used for determination of glutathione (GSH), [12] protein carbonyl (PC), [13] and sialic acid levels, [14] catalase (CAT), [15] superoxide dismutase (SOD), [16] glutathione-S-transferase (GST), [17] glutathione reductase (GR), [18] paraoxonase (PON), [19] xanthine oxidase (XO), [20] adenosine deaminase (ADA), [21] acetylcholine esterase (AChE), [22] lactate dehydrogenase (LDH), [23] and myeloperoxidase (MPO) [24] activities, total antioxidant capacity (TAC), [25] total oxidant status (TOS), [26] and reactive oxygen species (ROS) [27] levels. The protein levels of brain samples were determined according to the Lowry et al method.…”

Probucol improves erectile function by regulating endoplasmic reticulum stress in rats with streptozotocin‐induced diabetes

“…As unfolded or misfolded proteins accumulate in the endoplasmic reticulum, GRP78 located on the endoplasmic reticulum membrane is attracted to and binds to unfolded proteins, promoting proper protein folding.GRP78 is released via three endoplasmic reticulum stress sensors, pancreatic endoplasmic reticulum kinase‐like kinase (PERK), activating transcription factor 6 (ATF6), and inositol‐requiring enzyme 1 (IRE1), to maintain endoplasmic reticulum homoeostasis (Grootjans et al., 2016). However, when hyperglycaemia persists for an excessive length of time or when excessive stress occurs, the activation of endoplasmic reticulum stress induces the expression of apoptosis‐related proteins, including CHOP (Wang et al., 2009), which is considered a characteristic biomarker of endoplasmic reticulum stress‐induced apoptosis (Zhang et al., 2018). According to previous studies, PERK signals persist in the pro‐apoptotic phase, while in cells undergoing long‐term ER stress, IRE1α‐XBP1 and ATF6 pathways are inhibited (Hetz, 2012).…”

“…Probucol was recently shown to reduce endoplasmic reticulum stress and subsequent hepatic steatosis induced by endoplasmic reticulum stress (Chen et al., 2016). Meanwhile, as shown in the study by Zhang and colleagues, eliminating ER stress significantly improves erectile function in diabetic rats (Zhang et al., 2018). However, the relationship between probucol and ER stress in the cavernous body of the penis in diabetic rats has not been investigated.…”

“…Moreover, these pathological processes were recently suggested to be related to ER stress (Delbrel et al., 2018; Incalza et al., 2018). Therefore, approaches eliminating ER stress potentially represent a novel strategy to treat DMED (Zhang et al., 2018).…”