The effects of berberine and curcumin on cardiac, lipid profile and fibrosis markers in cyclophosphamide-induced cardiac damage: The role of the TRPM2 channel.

Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP-induced cardiac damage. Thirty-six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin-I, Creatine kinase-myocardial band (CK-MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP-ribose) polymerase-1 (PARP-1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme-linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein-1 (FSP1), transforming growth factor-beta- 1 (TGF-ß1) and α-smooth muscle actin (α-SMA) expressions were determined in heart tissue. The CYP group's troponin-I, total cholesterol, triglyceride, CK-MB, ROS, PARP-1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP-induced pathological damage, TRPM2, FSP1, TGF-ß1 and α-SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF-ß1, FSP1 and α-SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP-induced cardiac damage.

Effects of 3.5-GHz radiofrequency radiation on energy-regulatory hormone levels in the blood and adipose tissue.

In recent years exposure of living beings to radiofrequency radiation (RFR) emitted from wireless equipment has increased. In this study, we investigated the effects of 3.5-GHz RFR on hormones that regulate energy metabolism in the body. Twenty-eight rats were divided into four groups: healthy sham (n = 7), healthy RFR (n = 7), diabetic sham (n = 7), and diabetic RFR (n = 7). Over a month, each group spent 2 h/day in a Plexiglas carousel. The rats in the experimental group were exposed to RFR, but the sham groups were not. At the end of the experiment, blood and adipose tissues were collected from euthanized rats. Total antioxidant, total oxidant, hydrogen peroxide, ghrelin, nesfatin-1, and irisin were determined. Insulin expression in pancreatic tissues was examined by immunohistochemical analysis. Whole body specific absorption rate was 37 mW/kg. For the parameters analyzed in blood and fat, the estimated effect size varied within the ranges of 0.215-0.929 and 0.503-0.839, respectively. The blood and adipose nesfatin-1 (p = 0.002), blood and pancreatic insulin are decreased, (p = 0.001), gherelin (p = 0.020), irisin (p = 0.020), and blood glucose (p = 0.040) are increased in healthy and diabetic rats exposed to RFR. While nesfatin-1 are negatively correlated with oxidative stress, hyperglycemia and insulin, ghrelin and irisin are positively correlated with oxidative stress and hyperglycemia. Thus, RFR may have deleterious effects on energy metabolism, particularly in the presence of diabetes.

Uroprotective effects of berberine and curcumin in cyclophosphamide-induced interstitial cystitis.

In this study, it was aimed to investigate the effects of berberine (BER) and curcumin (CUR) in the experimental model of cystitis induced by cyclophosphamide (CYP). A total of 36 Wistar-Albino female rats were used in the study. Rats were randomly divided into six groups (n = 6). Normal control group, dimethyl sulfoxide (DMSO) group, CYP group (75 mg/kg), CYP + BER (75 mg/kg CYP and 50 mg/kg BER), CYP + CUR group (75 mg/kg CYP and 50 mg/kg CUR), CYP + BER + CUR group (75 mg/kg CYP and 50 mg/kg BER and 50 mg/kg CUR). Severe edema, hyperemia, hemorrhage, necrosis, and thinning of the epithelial layer were observed in the CYP group. BER and CUR treatment significantly reduced these pathologies. Masson-Trichrome staining was severe in the CYP group and moderate in the CYP + BER, CYP + CUR, and CYP + BER + CUR groups. In the CYP group, there was a severe expression of caspase-3, TNF-α and IL-6, and mild expression of IL-10. BER and CUR treatment decreased the expression of caspase-3, TNF-α, and IL-6 and increased the expression of IL-10. The findings of the study reveal that BER and CUR treatments may reduce CYP-induced bladder damage by reducing apoptosis and inflammation and ameliorating histopathological changes.

Biochemical and histopathological evaluation of systemic and ocular toxicity of favipiravir in rats.

Purpose: Favipiravir (FAV) used against COVID-19 is an antiviral drug that causes adverse reactions, such as hyperuricaemia, liver damage, and hematopoetic toxicity. The aim of the study was to investigate the systemic and ocular side-effects of FAV in rats, for the first time.Materials and methods: A total of 18 albino male Wistar rats were used in the study. The rats were divided into 3 groups as the healthy group (HG), the group given 50 mg/kg/day favipiravir (FAV50), and the group given 200 mg/kg/d favipiravir (FAV200). These doses were given to the experimental groups for one week. At the end of the experiment histopathological examinations were performed on the conjunctiva and sclera of the eye. In addition, malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), interleukin-1ß (IL-1ß), and tumor necrosis factor alpha (TNF-α) levels were measured in blood samples taken from rats. Results: Compared to HG, the MDA (1.37 ± 0.61 vs. 4.82 ± 1.40 µmol/mL), IL-1ß (2.52 ± 1.14 vs. 6.67 ± 1.99 pg/mL), and TNF-α levels (3.28 ± 1.42 vs. 8.53 ± 3.06 pg/mL) of the FAV200 group were higher. The levels of tGSH (7.58 ± 1.98 vs. 2.50 ± 0.98 nmol/mL) and SOD (13.63 ± 3.43 vs. 3.81 ± 1.43 U/mL) the FAV200 group were lower than the HG (p < 0.05, for all). The degree of damage to the cornea and sclera of the FAV200 group was quite high according to HG (p < 0.001). Conclusions: FAV can cause damage to rat conjunctiva and sclera by increasing oxidant stress and inflammation at high dose.

The protective effect of curcumin on cardiac markers and fibrosis in abemaciclib-induced cardiac damage in rats.

Abemaciclib (ABE) is a cyclin-dependent kinase inhibitor used in combination with an antiestrogen in the treatment of breast cancer. In addition to the important therapeutic properties of this drug, its side effects are not fully known. In this study, we aimed to investigate the protective effect of curcumin (CUR) on cardiac damage caused by ABE administration. Forty rats were equally divided into control, dimethyl sulfoxide (150 µL), CUR (30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CUR (26 mg/kg/day ABE and 30mg/kg/day CUR) groups (n = 8). Injections were administered daily for 28 days. Troponin-I, total cholesterol, and creatine kinase myocardial band (CK-MB) levels and cardiac fibrosis were higher in the ABE group than in the control group (p < 0.05), and were lower in the ABE + CUR group than in the ABE group (p < 0.05). The results showed that ABE administration can cause cardiac damage and increase cardiac fibrosis. However, they showed that coadministration of CUR with ABE could suppress increases in CK-MB, troponin-I, and total cholesterol levels and also cardiac fibrosis associated with cardiac damage. Therefore, we can infer that the subsequent administration of CUR ABE treatment can be used as a therapeutic strategy for preventing cardiac damage.

Molecular mechanism of the protective effect of adenosine triphosphate against paracetamol-induced liver toxicity in rats.

Toxic doses of paracetamol are also known to be close to therapeutic doses. This study aimed to biochemically investigate the protective effect of ATP against paracetamol-induced oxidative liver injury in rats and to examine the tissues histopathologically. We divided the animals into the paracetamol alone (PCT), ATP + paracetamol (PATP), and healthy control (HG) groups. Liver tissues were examined biochemically and histopathologically. Malondialdehyde level, AST and ALT activity in the PCT group were significantly higher than those in the HG and PATP groups (p < 0.001). The glutathione (tGSH) level, superoxide dismutase (SOD) and catalase (CAT) activity in the PCT group was significantly lower than that in the HG and PATP groups (p < 0.001), while animal SOD activity was significantly different between the PATP and HG groups (p < 0.001). The activity of CAT was almost the same. In the group treated with paracetamol alone, lipid deposition, necrosis, fibrosis, and grade 3 hydropic degeneration were observed. No histopathological damage was observed of the ATP-treated group, except for grade 2 edema. We discovered that ATP reduces the oxidative stress caused by paracetamol ingestion and protects against paracetamol-induced liver injury at the macroscopic and histological levels.

Protective role of resveratrol and apigenin against toxic effects of bisphenol a in rat salivary gland.

OBJECTIVES: The aim of this study was to investigate the cellular changes caused by Bisphenol A (BPA) exposure in salivary gland cells and to examine the protective role of resveratrol (RSV) and apigenin (APG) molecules against the negative effects of BPA. MATERIALS AND METHODS: Forty-two rats were randomly divided into 6 groups as; (i) control, (ii) BPA (130 mg/kg), (iii) BPA + RSV100 (100 mg/kg), (iv) BPA + RSV200 (200 mg/kg), (v) BPA + APG100 (100 mg/kg), and (vi) BPA + APG200 (200 mg/kg). In all experimental groups, the chemicals were given by gavage every day for a total of 28 days. RESULTS: The BPA administration caused a significant increase in tissue oxidative stress parameters as opposed to a significant decrease in tissue antioxidant levels (p < 0.05). On the other hand, it was observed that RSV and APG treatment reversed this situation (p < 0.05). The BPA administration did not cause a significant change in tissue prostaglandin E2 (PGE2) and nitric oxide levels, whereas low-dose RSV significantly reduced the tissue PGE2 levels compared to BPA (p < 0.05). BPA caused cytopathological changes and apoptosis in salivary gland cells. In the BPA group, edema, nuclear pleomorphism, and pyknotic nuclei were observed. Moreover, both RSV and APG were found to provide protection against BPA-induced cellular damage, while RSV provided better cellular protection than APG. The control group had a normal histological structure. CONCLUSION: BPA caused cytopathological changes and apoptosis in salivary gland cells. As a result, it was observed that these phytochemicals probably have cytoprotective effects in BPA intoxication.

Effect of curcumin on lipid profile, fibrosis, and apoptosis in liver tissue in abemaciclib-administered rats.

Abemaciclib (ABEM) is an important antitumor agent for breast cancer treatment. However, the side-effects of ABEM are unclear in the liver. This study investigated the protective effect of curcumin (CURC) on liver damage caused by ABEM. The rats were divided into five groups with eight animals in each group; Control, DMSO (150 µL for per rats), CURC, 30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CURC (26 mg/kg/day ABE, 30 mg/kg/day) groups. Injections were administered daily for 28 days. The levels of AST, LDH, HDL, LDL, triglyceride, and total cholesterol in serum, and hepatic tissue fibrosis, caspase-3, Bax, and TNF-α expression were higher in the ABE group compared to the control group (p < 0.05). Also, these parameters in the ABEM + CURC group were lower than in the ABE group (p < 0.05). The results showed that ABE administration could cause liver damage and increase fibrosis in the liver. In addition, it was shown that co-administration of CURC with ABE could suppress the levels of AST, LDH, HDL, LDL, triglyceride, and total cholesterol in serum, and fibrosis, caspase-3, Bax, and TNF-α expressions in the liver. These data are the first in the literature. Therefore, the administration of CURC following ABE may be a therapeutic agent in preventing liver damage.

Histological evaluation of the debris removal efficiency of activation of sodium hypochlorite solution at different concentrations.

BACKGROUND: This study aims to histologically evaluate the efficiency of debris removal through activation of 2.5% and 5.25% NaOCI using laser, ultrasonic, and intracanal heating methods. METHODS: Sixty-four maxillary central incisor teeth were randomly divided into two groups according to the irrigation solution (n = 32); 2.5% NaOCI and 5.25% NaOCI. Subsequently, the samples were further divided into four subgroups according to the final irrigation activation technique (n = 8); SubgroupA: Er,Cs:YSGG laser, SubgroupB: Ultrasonic, Subgroup C: Intracanal heating, Subgroup D: no activation. Generalized Linear Models and Bonferroni tests were used for statistical analysis (p < 0.05). RESULTS: The effect of NaOCI concentration was statistically significant (p < 0.001). Furthermore, the activation of NaOCI by laser exhibited a statistically significant difference compared to the ultrasonic and intracanal heating methods (p < 0.001). CONCLUSION: The efficiency of root canal cleaning increases with higher NaOCI concentration. Activation of NaOCI also significantly enhances its effectiveness.

Sinapic acid ameliorates cisplatin-induced disruptions in testicular steroidogenesis and spermatogenesis by modulating androgen receptor, proliferating cell nuclear antigen and apoptosis in male rats.

The chemotherapeutic cisplatin, which is widely used in many cancer types, causes testicular toxicity. Sinapic acid has many therapeutic effects such as antioxidant, anti-inflammatory and antihyperglycaemic. This study aimed to investigate the improving effects of sinapic acid in cisplatin-induced testicular toxicity. Twenty-eight rats were distributed into 4 groups. Control group: saline was applied intraperitoneal. Cisplatin group: A single dose of 7 mg/kg of cisplatin was injected into rats. Cisplatin +Sinapic acid group: 3 days after a single dose of 7 mg/kg cisplatin was injected, 25 mg/kg of sinapic acid was given for 7 days. Sinapic acid group: rats were received 25 mg/kg/day of sinapic acid. Numerical density of spermatogonium, Leydig and volume density of germinal epithelial were calculated. Caspase-3, Bcl-2, AR and PCNA expressions in testis were evaluated and testosterone and LH levels were measured. Cisplatin application decreased the numerical density of spermatogonium and Leydig, volume density of germinal, epididymal sperm count, testosterone, LH and the expressions of Bcl-2, AR and PCNA in testis. However, sinapic acid treatment significantly restored the parameters of our study. The results of the present study revealed that cisplatin can cause male reproductive toxicity and sinapic acid can have improving effects against cisplatin-induced male reproductive toxicity.

Effect of low and high dose of favipiravir on ovarian and reproductive function in female rats: Biochemical and histopathological evaluation.

Favipiravir is a drug which shows antiviral activity by inhibiting RNA-dependent RNA polymerase. Favipiravir causes severe adverse effects at high doses. The aim of this study was to investigate the effects of low and high dose favipiravir on ovarian and reproductive function in female rats. The rats were divided into three groups: HG group (healthy rats), FAV-100 group (rats administered 100 mg/kg favipiravir), and FAV-400 group (rats administered 400 mg/kg favipiravir) with 12 rats in each group. Favipiravir was administered orally twice daily for 1 week. Six rats from each group were euthanized and their ovaries were removed. Oxidative and antioxidant parameters were measured in ovarian tissues and examined histopathologically. The remaining animals were kept to breed. Animals receiving favipiravir had increased oxidant content, decreased antioxidant activity, decreased histopathological damage, infertility, and gestational delay. Favipiravir treatment should be used with caution, especially in women of reproductive age.

Evaluation of protective effects of gallic acid on cisplatin-induced testicular and epididymal damage.

Cisplatin is an effective chemotherapeutic drug used to treat many types of tumours. However, it may cause male reproductive toxicity. Gallic acid exhibits beneficial effects such as antioxidant, anti-inflammatory and antitumor. The current study investigated the beneficial effects of gallic acid against testis and epididymis toxicity induced by cisplatin. Male rats were divided into 4 groups as follows (n = 7): Control, cisplatin (a single dose of 8 mg/kg), Gallic acid (50 mg/kg) and cisplatin +Gallic acid groups. Testis was examined morphometrically by stereological methods. In addition, apoptosis, DNA damage, oxidative stress parameters in testis and testosterone in serum were measured. Epididymis was histopathologically evaluated. As a result, a significant decrease was observed in the number of spermatogonia, Leydig and Sertoli cells, testicular volume, height of germinal epithelial, Bcl-2 immunopositive cell number, activity of CAT, GSH and SOD enzymes and serum testosterone levels compared with the cisplatin group control group, while a significant increase was observed in the number of Caspase-3, Bax and 8-OHdG immunopositive cells and the MDA levels. However, Gallic acid significantly restored these parameters. Our study reveals that Gallic acid may improve Cisplatin-induced male reproductive toxicity by reducing oxidative stress, suppressing apoptosis and DNA damage and restoring structural and functional deterioration.

The effects of CoQ10 supplement on matrix metalloproteinases, oxidative DNA damage and pro-inflammatory cytokines in testicular ischaemia/reperfusion injury in rats.

We aimed to study the effect of coenzyme Q10 on pro-inflammatory cytokine, matrix metalloproteinase, oxidative DNA damage, caspase 3 and caspase 8 in ischaemia/reperfusion injury led to by testicular torsion/detorsion. Our research is a controlled experimental animal research using rats. This study was conducted with fifty-six adult male Albino Wistar rats. Interleucine-1ß, 2, 6, 10, tumour necrosis factor-α, matrix metalloproteinase-2, 3, 9, 13, tissue inhibitor matrix metalloproteinase-1, 2, malondialdehyde and leucocyte 8-hydroxy-2-deoxy guanosine/106 deoxyguanosine was detected in serum and tissue samples. In addition, immunohistochemical analysis of caspase 2 and caspase 8 was performed. In testicular I/R injury, especially 24 hr after detorsion, oxidative damage pro-inflammatory cytokines and matrix metalloproteinases were increased. At the coenzyme Q10 group, a meaningful decrease was observed in these parameters. In addition, a decrease in the expression of caspase3 and caspase 8 was viewed in coenzyme Q10-treated groups. The coenzyme Q10 has beneficial effects on oxidative damage, pro-inflammatory cytokine levels, remodelling of extracellular matrix and apoptosis in testicular I/R injury.

Whole-Mount Immunohistochemical and Immunofluorescence Assays in Zebrafish Embryos.

Zebrafish embryos are an important organism used as an in vivo model in a wide variety of disciplines from the past to the present. Immunohistochemistry analyses are an important method used to determine the localization of specific antigens in tissue sections with labeled antibodies depending on antigen-antibody interactions in zebrafish embryos. Immunofluorescence assays are an immunohistochemistry method that uses fluorophores to determine diverse cellular antigens. Zebrafish embryos and larvae, with their small size, are the most ideal model organisms for whole-mount immunohistochemical and immunofluorescent methods today. The small size of these organisms allows simultaneous evaluation of different tissues and organs, and results are obtained in a shorter time. In this section, whole-mount immunohistochemical and immunofluorescent analysis methods in zebrafish embryos, and larvae are summarized in detail, taking into account different studies and recent advances.

Protective Action of Curcumin and Alpha-lipoic Acid, Against Experimental Ultraviolet-A/B Induced Dermal-injury in Rats.

The objective of this study was to examine the therapeutic efficacy of curcumin (CUR) and α-lipoic acid (ALA) in mitigating UV-A and UV-B-induced damage (UVAB) in rat dorsal skin. This was achieved through the utilisation of immunohistochemical (TUNEL), biochemical and stereological techniques. The rats in the UVAB, UVAB + CUR, and UVAB + ALA groups were subjected to UVAB irradiation for a period of two hours per day over the course of one month. The UVAB + CUR and UVAB + ALA groups were administered 100 mg/kg/day of curcumin and 100 mg/kg/day of α-lipoic acid via gavage 30 min prior to UVAB irradiation. The CUR group was administered 100 mg/kg/day of curcumin via gavage, while the ALA group received the same dose of α-lipoic acid. A significant change in the volume ratio of the dorsal skin epidermis and dermis was observed in the stereological findings of the rats in the UVAB group. These changes exhibited a favourable progression as a consequence of the CUR and ALA applications. In the UVAB group, TOS and OSI were significantly elevated as a consequence of the rise in oxidative stress. Conversely, the treatment groups demonstrated a notable reduction in TOS and OSI levels. The study also revealed a substantial increase in the number of apoptotic cells within the UVAB group. However, the treatment groups exhibited a significant decline in apoptotic cells. In conclusion, the findings suggest that CUR and ALA possess a protective effect against UVAB-induced skin damage.

Effect of abemaciclib and curcumin administration on sex hormones, reproductive functions, and oxidative DNA expression in rats.

This study investigated whether abemaciclib (ABE) administration had any adverse effects on ovarian and sex hormones in female rats, and the protective effect of curcumin. Forty female rats were equally divided into the sham control, DMSO, curcumin (CMN), ABE, and ABE+CMN groups. Pharmaceuticals were administered by gavage daily for 28 days. Serum sex hormones were measured in an autoanalyzer operating with a microparticle immunoassay method. In addition, histopathological examination and 8-OHdG expression were performed on the ovarian tissue. Progesterone and testosterone levels were significantly decreased, while estradiol levels were significantly increased, in the ABE group compared to the sham and DMSO groups. In addition, there were significant differences in sex hormone levels in the CMN and/or CMN+ABE groups compared to the ABE group. There was decreased expression of 8-OHdG in the ABE+CMN group compared to the ABE or CMN only groups. This study exhibited that ABE administration can adversely affect functions and histology of the ovarian tissue, but CMN therapy may be protective against the adverse effects on ovarian in ABE-induced rats.

Sinapic acid alleviates cisplatin-induced acute kidney injury by mitigating oxidative stress and apoptosis.

Cisplatin is an anticancer agent with many side effects such as nephrotoxicity, as well as being widely used in the treatment of many tumor types. Sinapic acid has antioxidant, anti-inflammatory, antihyperglycemic, and antiapoptotic effects. This study aimed to investigate the possible beneficial effects of sinapic acid against cisplatin-induced nephrotoxicity. Twenty-eight Wistar albino male rats were used. The groups are as follows: control, cisplatin, cisplatin + sinapic acid, and sinapic acid groups (n = 7). The control group received 1 ml of single-dose intraperitoneal saline on the first day of the study. The cisplatin group was given a single dose of 7 mg/kg cisplatin intraperitoneal. Animals in the cisplatin + sinapic acid group were given sinapic acid for 7 days 25 mg/kg, 3 days after oral gavage administration of 7 mg/kg cisplatin intraperitoneal. The sinapic acid group was given 25 mg/kg/day of sinapic acid by oral gavage for 7 days after the 3rd day of the study. The kidney of the rats was examined by stereological, immunohistochemical, histopathological, and biochemical methods. According to the stereological findings of the study, while the volume of the glomerulus cortex and filtration gap increased, the volume of the medulla decreased, and there was no significant difference in tubular volume in the CP group compared to the control group. The volume of the glomerulus, cortex, and filtration gap of the cisplatin + sinapic acid group was significantly reduced compared to the cisplatin group (p˂0.05). Histopathologically, it was observed the enlargement of the filtration gap, tubular dilatation, atrophy, renal fibrosis, deterioration of the microvilli, and necrosis in the tubular epithelial cells in the cisplatin group. In the cisplatin + sinapic acid group, these pathologies decreased compared to the cisplatin group. Compared to the control group, caspase-3 expression, urea, creatine, and malondialdehyde increased, while Bcl-2 and catalase decreased in the cisplatin group. However, caspase-3 expression, urea, creatine, and malondialdehyde were decreased, while Bcl-2 and catalase increased in the cisplatin + sinapic acid group compared to the cisplatin group. The results of our study showed that sinapic acid reduced the nephrotoxicity induced by cisplatin.

Evaluation of the effects of sinapic acid and ellagic acid on sciatic nerve in experimental diabetic rats by immunohistochemical and stereological methods.

In our study, we aimed to examine the effects of sinapic acid and ellagic acid on neuropathy caused by diabetes in peripheral nerves. Fifty-six adult Wistar Albino rats Control, Diabetes, Diabetes+Sinapic Acid, Diabetes+Ellagic Acid, Diabetes+Sinapic Acid+Ellagic Acid, Sinapic Acid, Ellagic Acid and as Sinapic Acid+Ellagic Acid, they were randomly divided into eight groups(n:7). A single dose of 50 mg/kg streptozotocin(STZ) was administered intraperitoneally to the groups to be diagnosed with diabetes. Diabetes was accepted as blood glucose value of 250 mg/dL and above. Streptozotocin was given to the diabetes groups, 20 mg/kg/day intragastric Sinapic acid to the Sinapic acid groups, 50 mg/kg/day intragastric Ellagic acid to the Ellagic acid groups for 28 days. At the end of the experiment, 0.5 cm of the right sciatic nerve was removed. It was fixed in 10% formaldehyde. After histological follow-up, it was embedded in paraffin, 5 µm thick sections were taken. Immunohistochemical staining with Fibrinogen alpha, Laminin ß-1 and Collagen IV antibodies and stereological evaluation was performed by Physical Dissector Combination method. Collagen IV was used in control, diabetes and treatment groups showed similar immunostaining. Fibrinogen alpha was observed to be increased in the vessel wall in the diabetes group, while the uptake was minimal in the control and treatment groups. While Laminin ß-1 was increased in the diabetes group compared to the control group, immunostaining was observed in the treatment groups similar to the control group. It was observed that the total nerve area diabetes group decreased significantly compared to the control group, and the treatment groups, except for D+EA group were similar to the control group, but there was no statistically significant difference. The axon numbers in the diabetes group decreased significantly compared to the control group, and the treatment groups were similar to the control group, and there was no statistically significant difference (P > 0.05). It was determined that Sinapic Acid and Ellagic acid had positive effects on the nervous tissue in diabetic neuropathy.

Involvement of TRPM2 Channel on Doxorubicin-Induced Experimental Cardiotoxicity Model: Protective Role of Selenium.

Doxorubicin (DOXR) is an important chemotherapeutic drug used in cancer treatment for many years. Several studies reported that the use of DOXR increased toxicity by causing an increase in oxidative stress (OS), especially in the heart. In this study, we investigated the protective effect of selenium (Se) and the role of transient receptor potential melastatin-2 (TRPM2) channel activation by using N-(p-amylcinnamoyl) anthranilic acid (ACA) in a model of DOXR-induced cardiotoxicity. Sixty female rats were equally divided into the control, dimethyl sulfoxide (DMSO), DOXR, DOXR + Se, DOXR + ACA, and DOXR + Se + ACA groups. Glutathione (GSH), glutathione peroxidase (GSH-Px), caspases (Cas) 3 and 9, interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), poly [ADP-ribose] polymerase 1 (PARP-1), and TRPM2 channel levels were measured by ELISA. In addition, histopathological examination was performed in cardiac tissues and TNF-α, caspase 3, and TRPM2 channel expression levels were determined immunohistochemically. The levels of GSH, GSH-Px, caspases 3 and 9, IL-1ß, TNF-α, ROS, PARP-1, and TRPM2 channel in serum, and cardiac tissue in the DOXR group were higher than in the control and DMSO groups (p < 0.05). However, these parameters in Se and/or ACA treatment groups were lower than in the DOXR group (p < 0.05). Also, we determined that Se and/or ACA treatment together with DOXR application decreased the TNF-α, Cas-3, and TRPM2 channel expression levels in the cardiac tissue. The data showed that administration of Se and/or ACA treatment together with DOXR may be used as a therapeutic agent in preventing DOXR-induced cardiotoxicity.

Effect of Hesperidin on Sciatic Nerve Damage in STZ-Induced Diabetic Neuropathy: Modulation of TRPM2 Channel.

Diabetic neuropathy (DNP) is a severe complication of diabetes mellitus. In this study, we examined the potential of hesperidin (HES) to attenuate DNP and the involvement of the TRPM2 channel in this process. The rats were given a single dose of 45 mg/kg of streptozotocin (STZ) intraperitoneally to induce diabetic neuropathic pain. On the third day, we confirmed the development of diabetes in the DNP and DNP + HES groups. The HES groups were treated with 100 mg/kg and intragastric gavage daily for 14 days. The results showed that treatment with HES in diabetic rats decreased STZ-induced hyperglycemia and thermal hyperalgesia. Furthermore, in the histopathological examination of the sciatic nerve, HES treatment reduced STZ-induced damage. The immunohistochemical analysis also determined that STZ-induced increased TRPM2 channel, type-4 collagen, and fibrinogen immunoactivity decreased with HES treatment. In addition, we investigated the TRPM2 channel activation in the sciatic nerve damage mechanism of DNP model rats created by STZ application using the ELISA method. We determined the regulatory effect of HES on increased ROS, and PARP1 and TRPM2 channel activation in the sciatic nerves of DNP model rats. These findings indicated that hesperidin treatment could attenuate diabetes-induced DNP by reducing TRPM2 channel activation.