Effect of selenium against doxorubicin-induced oxidative stress, inflammation, and apoptosis in the brain of rats: Role of TRPM2 channel

Doxorubicin (DOX) is widely used as an anticancer drug in humans' various solid and haematological tumours. Although many studies on the toxic effect of DOX are used in different organs, its impact on brain tissue has yet to be adequately studied. This study investigated the protective effect of selenium (Se) and the role of transient receptor potential melastatin?2 (TRPM2) channel activation against brain damage caused by DOX administration. Sixty rats were randomly divided into the sham, dimethyl sulfoxide (DMSO), DOX, DOX?+?Se, DOX?+?N-(p-amylcinnamoyl) anthranilic acid (ACA), and DOX?+?Se?+?ACA groups. The reactive oxygen species (ROS), poly [ADP-ribose] polymerase 1 (PARP1), and TRPM2 channel levels in brain tissues were measured by ELISA. In addition, a histopathological examination was performed in the cerebral cortex and hippocampal areas, and the TRPM2 channel, NF-?B, and caspase-3 expression were determined immunohistochemically. The levels of ROS, PARP1 and TRPM2 channel in the DOX group were higher than in the sham and DMSO groups (P <?0.05). However, these parameters were decreased in the in DOX+Se and DOX+ACA groups by the treatments of Se and ACA (P?<?0.05). Also, we determined that Se and ACA treatment decreased the NF-?B, caspase-3, and TRPM2 channel expression in the cerebral cortex and hippocampal areas in the DOX-induced rats. The data showed that Se and/or ACA administration together with DOX administration could be used as a protective agent against DOX-induced brain damage.

Relationship with Nephrotoxicity of Abemaciclib in Rats: Protective Effect of Curcumin

Abemaciclib (ABE) has been reported to cause gastrointestinal toxicity. Therefore, it is important to investigate the question of whether abemaciclib administration causes nephrotoxicity in the gastrointestinal tract, and if so, what pathophysiological pathways it follows. In this study, the relationship between ABE administration and nephrotoxicity and the protective effect of Curcumin (CMN) was investigated. Forty female rats were equally divided into the sham, dimethyl sulfoxide (DMSO), CMN, abemaciclib and ABE+CMN groups. Aquaporin (AQP) 1-7, TNF-?, IL-1?, intercellular adhesion molecule (ICAM)-1, IL-10 and IL-37 levels in serum and kidney tissue homogenates were measured by ELISA. In addition, Urea and Creatinine were measured in serum samples. Furthermore, histopathological examination was performed in kidney tissues and Bax, Caspase-3 and Bcl-2 expression levels were determined immunohistochemically. The levels of AQP1-7 and IL-10 in the ABE group were partially lower than in the other groups, while the ratio of TNF?, IL-1?, MDA, caspase-3 and Bax/Bcl2 were high. In addition, kidney tissue was examined histopathologically. However, AQP1 and 7 levels in the ABE+CMN group were higher than in the ABE group, while TNF-?, IL-1?, MDA, Caspase-3 levels and Bax/Bcl2 ratio were low. In addition, the poor histopathological changes in the ABE group were largely restored in the ABE+CMN. The data presented that ABE in rats can adversely affect functions and histology of kidneys through the increase in oxidative stress, pro-inflammatory cytokines and apoptosis, but CMN therapy may be protective against the nephrotoxic effects of ABE

Evaluation of serum ghrelin, nesfatin-1, irisin, and vasoactive intestinal peptide levels in temporal lobe epilepsy patients with and without drug resistance: a cross-sectional study

SUMMARY OBJECTIVE: Epilepsy is a common disorder that affects the nervous systems of 1% of worldwide population. In epilepsy, one-third of patients are unresponsive to current drug therapies and develop drug-resistant epilepsy. Alterations in ghrelin, nesfatin-1, and irisin levels with epilepsy were reported in previous studies. Vasoactive intestinal peptide is among the most common neuropeptides in the hippocampus, which is the focus of the seizures in temporal lobe epilepsy. However, there is also lack of evidence of whether these four neuropeptide levels are altered with drug resistant temporal lobe epilepsy or not. The aim herein was the evaluation of the serum levels of nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide in drug-resistant temporal lobe epilepsy patients and temporal lobe epilepsy (TLE) without drug resistance, and to compare them to healthy controls. METHODS: This cross-sectional study group included 58 temporal lobe epilepsy patients (24 with drug resistant temporal lobe epilepsy and 34 with temporal lobe epilepsy who were not drug-resistant) and 28 healthy subjects. Nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide serum levels were determined using enzyme-linked immunosorbent assay. RESULTS: The serum ghrelin levels of patients with drug resistant temporal lobe epilepsy were seen to have significantly decreased when compared to those of the control group (p<0.05). Serum nesfatin-1, vasoactive intestinal peptide, and irisin levels were seen to have decreased in the drug resistant temporal lobe epilepsy group when compared to those of the control and temporal lobe epilepsy groups; however, the difference was non-significant (p>0.05). CONCLUSIONS: The results herein suggested that ghrelin might contribute to the pathophysiology of drug resistant temporal lobe epilepsy. However, further studies are needed to confirm this hypothesis.

Do avanafil and zaprinast exert positive effects on bone tissue via the nitric oxide/cyclic guanosine monophosphate/protein kinase-G signaling pathway in rats with ovariectomy-induced osteoporosis?

Phosphodiesterase-5 inhibitors (PDE-5Is) exert positive effects on bone healing and mineralization by activation the nitric oxide/cyclic guanosine monophosphate/protein kinase-G (NO/cGMP/PKG) signaling pathway. In this study, the effects of zaprinast and avanafil, two PDE-5Is, on the NO signaling pathway, estrogen levels, selected bone formation and destruction marker levels, whole-body bone mineral density (WB-BMD), right femur trabecular bone thickness (RF-TBT) and epiphyseal bone width, angiogenesis in the bone-marrow, and selected oxidative stress parameter levels were investigated in rats with ovariectomy-induced osteoporosis. Twenty four adult rats (8 months old) were equally divided into four groups. The first group was the sham operated group. Groups 2, 3 and 4 included ovariectomized rats. At six months after ovariectomy, the 3rd and 4th groups were administered 10 mg/kg zaprinast and avanafil daily as a single dose for 60 days, respectively. Increases in the activity of the NO/cGMP/PKG signalling-pathway, C-terminal collagen peptide levels, angiogenesis in the bone marrow, RF-TBT, epiphyseal bone width and WB-BMD were observed compared to the ovariectomized positive control group (OVX), while the pyridinoline and deoxypyridinoline levels were decreased in the OVX+zaprinast and OVX+avanafil groups (p<0.05). The malondialdehyde, ubiquinone10/ubiquinol10 and 8-hydroxy-2-deoxyguanosine/106deoxyguanosine levels were also increased in the ovariectomized groups compared to the sham group (p<0.05). Based on these results, the levels of bone atrophy and some markers of oxidative stress were increased due to acute estrogen deficiency induced by ovariectomy, but zaprinast and avanafil administration significantly prevented these changes

Radioprotective profile of Urtica dioica L. seed extract on oxidative DNA-damage in liver tissue and whole blood of radiation-administered rats

It was aimed to investigate the radioprotective activity of Urtica dioica L. seed extract (UDSE) in the whole blood and liver of radiation-administered rats, both biochemically and immunohistochemically. 32 rats were divided into 4 groups (n:8). Control group (C): no administration for 10 days. Radiation group (IR): fed pellets for 10 days after exposure to radiation. Radiation + UDSE (IR+UDSE) group: exposed to radiation and fed UDSE for 10 days. UDSE group (UDSE): fed UDSE for 10 days. Radiation (5Gy) was given as a single fraction. 8-hydroxy-2-deoxyguanosine (8-OHdG) and deoxyguanosine (dG) levels were analyzed by biochemical method and glutathione peroxidase 1 (GPx-1) analyses were performed by immunohistochemical method in the liver and blood tissues of the rats. The increased 8-OHdG rates and decreased GPx-1 immunoreactivity was observed in the IR group. Those parameters were ameliorated in the IR+UDSE group when compared to the IR group. UDSE is likely to be a valuable radioprotector against the harmful effects of radiation.

Protective effects of Urtica dioica L. seed extract on liver tissue injury and antioxidant capacity in irradiated rats

Radiotherapy is often used for the treatment of cancer. However, it causes some side effects in patients. This study aimed to determine the hepatoprotective effects of Urtica dioica L. seed-extract (UDSE) in radiation-induced liver injury. Thirty-two male rats were randomly divided into 4 groups (n=8): control(C) group: no action was taken; radiation (R) group: irradiation was administrated at 5Gy single-fraction, radiation with UDSE(R+UDSE) group: irradiation was administrated at 5 Gy single-fraction and animals were fed pellets with 30 mL UDSE/kg; UDSE group: animals were fed pellets with 30 mL UDSE/kg. All of the experiments were performed in all of the groups over 10 days. Malondialdehyde (MDA) and reduced-glutathione (GSH) levels and superoxide-dismutase (SOD), catalase (CAT), glutathione-peroxidase (GSH-Px), aspartate-transaminase (AST), and alanine-aminotransferase (ALT) activities were determined. Histopathological findings were also evaluated in liver tissues. SOD, CAT and GSH-Px activities and GSH levels in the serum and liver were significantly increased, while MDA levels decreased in the R+UDSE group compared with the R group (P<0.05). Moreover, AST and ALT serum activities in the R+UDSE group were lower than those in the R group (P<0.05). In addition, radiation induced degenerative/necrotic changes in the R group were significantly compensated in the R+UDSE group. The results showed that radiation increased oxidative stress and decreased antioxidant capacity, as well as degeneration in the liver. However, UDSE attenuated these degenerative changes.