The effect of baicalein on endoplasmic reticulum stress and autophagy on liver damage.

Carbon tetrachloride (CCl4) is a toxic chemical that causes liver injury. CCl4 triggers endoplasmic reticulum (ER) stress and unfolded protein response (UPR). UPR triggers autophagy to deal with the damage. The aim of this study was to investigate the effect of baicalein, derived from Scutellaria baicalensis, on CCl4-induced liver damage concerning ER stress and autophagy. Two groups of Wistar albino rats (n = 7/groups) were treated with 0.2 ml/kg CCl4 for 10 days with and without baicalein. Histological and transmission electron microscopy (TEM) analysis, autophagy, and ER stress markers measurements were carried out to evaluate the effect of baicalein. Histological examinations showed that baicalein reduced liver damage. TEM analysis indicated that baicalein inhibited ER stress and triggered autophagy. CCl4-induced elevation of C/EBP homologous protein (CHOP), glucose-regulating protein 78 (GRP78), activating transcription factor 4 (ATF4), activating transcription factor 6 (ATF6), inositol requiring enzyme 1 (IRE1), pancreatic ER kinase (PERK), and active/spliced form of X-box-binding protein 1 (XBP1s) ER stress markers were decreased by baicalein. Baicalein also increased the autophagy-related 5 (ATG5), Beclin1, and Microtubule-associated protein 1A/1B-light chain 3-phosphatidylethanolamine-conjugated form (LC3-II) autophagy marker levels. In conclusion, baicalein reduced the CCl4-induced liver damage by inhibiting ER stress and the trigger of autophagy.

Protective effect of betaine against skeleton muscle apoptosis in rats induced by chronic alcohol and statin consumption.

AIM: The aim of the present study was to investigate the effect of apoptosis on rat skeletal muscle caused by chronic alcohol and statin consumption with modified liquid diet and to elucidate protective effects of betaine supplementation. METHODS: TNF-α (tumor necrosis factor), NF-kB (Nuclear Factor kappa B), cytochrome c and caspase-3 levels with or without betaine treatment in alcohol and/or statin-induced skeleton muscle apoptosis rats as well as in controls were measured in serum and tissue. Histologic examinations of the muscle tissues were also performed. RESULTS: In our study, betaine treated treatment groups we found that calpain and caspase activities and cytokine c release were decreased caused by alcohol, statin and more importantly alcohol+statin group and TNF and NF-kB levels were also close to the levels of control group. Similarly, significant improvements have been observed in our morphological and histological examination results also supporting our biochemical data. CONCLUSION: We found that combined consumption of ethanol and statin is capable of triggering apoptotic cell death in rat muscles more than the consumption of only alcohol or only statin. Betaine was able to reduced this muscle cell death induced by alcohol and/or statin consumption (Tab. 4, Fig. 4, Ref. 43).

Potential protective effect of resveratrol on acoustic trauma: electron microscopy study.

OBJECTIVE: To investigate the potential preventive effect of resveratrol in rats exposed to acoustic trauma (AT). MATERIALS AND METHODS: In this experimental study, Wistar albino rats were divided into three groups: Group 1 (Control, n = 6), Group 2 (AT, n = 6), and Group 3 (resveratrol + AT). The rats in Group 2 were exposed to AT. The rats in Group 3 received resveratrol (300 mg/kg/day) via gavage for 7 days. On day 7, the rats were exposed to AT 10 min following resveratrol treatment. Histological sections of the cochleae were examined using light microscopy, transmission (TEM), and scanning electron microscopy (SEM). RESULTS: The cochlear hair cells, stereocilia, and Deiters' cells of the control group appeared normal in all microscopic evaluations. In Group 2, light microscopy revealed predominantly inner hair cell loss, although the outer hair cells were affected. TEM and SEM examination showed severe loss of stereocilia and SEM revealed stereocilia arranged in an asymmetric array. The cochlear structure in Group 3 appeared well preserved under the light microscope, and although TEM and SEM revealed stereocilia loss, the hair cells and stereocilia appeared near normal compared with those of Group 2. CONCLUSIONS: Resveratrol may have a protective effect against AT damage in the cochlea, most likely through its antioxidant activity. Our results may be useful for studies in humans exposed to AT and noise-induced hearing loss related to chronic exposure to occupational noise.

Effect of retinyl acetate on transglutaminase 2 activity in carcinogen treated rat liver.

Transglutaminase 2 (TG2) has been implicated in wound healing, cellular differentiation, apoptosis and cell survival. TG2 activity increases following acute and chronic liver injury; however, the role of TG2 in tumors, is controversial. TG2 is a retinoid-inducible enzyme. We investigated the effects of retinyl acetate (RA) on the activity and levels of TG2 during the initiation and promotion stages of liver cancer. p-Dimethylaminoazobenzene (p-DAB) was used as initiator and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) was used as promoter in our model of carcinogenesis. Rats were divided into four groups of 24: control, corn oil control, p-DAB + TCDD, and p-DAB + TCDD + RA. Six rats from each group were sacrificed at days 30, 60, 90 and 120. TG2 activity decreased in the p-DAB + TCDD treated group, but TG2 immunostaining scores did not change by days 90 and 120. Neither TG2 enzyme activity nor the immunostaining score of TG2 protein changed in the tissues of the p-DAB + TCDD + RA group by days 90 and 120. TG2 activity was not be ameliorated by RA during the initiation or promotion stages of carcinogen induced liver cancer.

Evaluation of the reproductive toxicity of naproxen sodium and meloxicam in male rats.

Nonsteroidal anti-inflammatory drugs that are cyclooxygenase (COX) enzyme inhibitors have generally been used in short-term pain management and also to treat inflammation chronically. It is known that COX enzyme and prostaglandins play important roles in the regulation of reproductive functions in females. However, there are relatively few studies for the male reproductive system, and the results of these studies are contradictory. In this study, sperm count and motility, COX-1, COX-2, prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), and prostaglandin F2α (PGF2α) levels in testis tissue, plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels, and histopathological examination of testis tissue were evaluated after naproxen sodium and meloxicam administration in male rats. Also, testis superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione (GSH) levels were measured to investigate the oxidation status. According to our results, sperm count and motility were significantly decreased in treatment groups. Plasma hormone levels did not show any statistical differences between the groups. COX-1, PGE2, and PGF2α levels were significantly decreased, while the decreases in COX-2 and PGE1 levels did not show any significance statistically. Testis SOD, catalase, GPx, and GSH levels were decreased significantly. According to the results of histopathological examination, damage in seminiferous tubules, where spermatogenesis developed, was observed. In conclusion, naproxen sodium and meloxicam decreased the sperm count and motility and also induced the damage of seminiferous tubules as a direct effect without affecting plasma hormone levels in our study. The mechanism of the reproductive toxicity induced by these agents may be based on the inhibition of prostaglandin synthesis and the induction of oxidative stress can be emphasized as a secondary factor.