Tissue Malondialdehyde Levels Research Articles

Use of Mesenchymal Stem Cells in Experimental Ovarian Damage.

Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis. The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage. Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (106 cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted. BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs. The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.

Evaluation of the protective effect of coenzyme Q10 against x-ray irradiation-induced ovarian injury.

This study focused on the anti-oxidant and anti-apoptotic effects of CoQ10 in ovaries exposed to pelvic radiation. Thirty-two female rats were randomly assigned into four groups. Group I (control group), Group II: Only 2 Gy pelvic x-ray irradiation (IR) was administered as a single fractioned dose. Group III: 30 mg/kg CoQ10 was administered by oral gavage +2 Gy pelvic IR. Group IV: 150 mg/kg CoQ10 was administered by oral gavage +2 Gy pelvic IR. CoQ10 treatment was started 7 days before pelvic IR and completed 7 days later. The rats in Group III and IV were treated with CoQ10 for a total of 14 days. Histopathological analysis showed severe damage to the ovarian tissue in the radiation group, while both doses of CoQ10 showed normal histological structure. Likewise, while there was a high level of staining in the IR group for necrosis and apoptosis, the CoQ10 treated ones were like the control group. Tissue Malondialdehyde (MDA) levels were like the control group in the low-dose CoQ10 group, while the MDA levels of the high dose CoQ10 group were similar to the radiation group. Usage of low-dose CoQ10 has a radioprotective effect on radiation-induced ovarian damage. Although the use of high doses is morphologically radioprotective, no antioxidative effect was observed in the biochemical evaluation.

Therapeutic Potential of Silymarin in Mitigating Paclitaxel-Induced Hepatotoxicity and Nephrotoxicity: Insights into Oxidative Stress, Inflammation, and Apoptosis in Rats.

Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits. To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways. Experimental animal model. The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models. SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05). Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.

Modulation of chronic hypoxia on ovarian structure, oxidative stress, and apoptosis in female Nile Tilapia (Oreochromis niloticus)

Chronic hypoxia in aquaculture impairs gonad growth and reduces the reproductive capacity of farmed fish. The aim of this study was to investigate how prolonged hypoxia affects gonad maturation, the degree of oxidative stress, and apoptosis in female Nile Tilapia. We conducted an 85-day experiment in which female Nile tilapia were cultured with dissolved oxygen (DO) levels of 6.0 ± 0.1, 4.0 ± 0.1, and 2.0 ± 0.1 mg/L, designated as the normal-DO group (NG), the low-DO group (LG), and the hypoxia-stressed group (HG), respectively. The results show that chronic hypoxia reduced the specific growth rate and gonadosomatic index of female Nile tilapia. The chronic hypoxia significantly affects the final body weight, weight gain rate, feed conversion ratio, hepatosomatic index and gonado somatic index, compared with the fish in the NG, those in the HG and LG had significantly lower values for all growth indicators (P < 0.05). The gonads of fish in the LG and HG did not reach maturity, whereas those of fish in the NG developed normally. This was related to their higher levels of follicle-stimulating hormone, luteinizing hormone, and estradiol, causing their oocytes to reach stages IV and V. In contrast, the majority of oocytes in fish in the LG were in stages II and III, and the presence of more atretic follicles in the ovary of fish in the HG indicated that their gonads were still immature. Compared with fish in the NG and LG, those in the HG showed increased malondialdehyde levels in ovarian tissues and decreased activities of superoxide dismutase and catalase. The transcript levels of genes related to the nrf2 signaling pathway (nrf2, keap1) and apoptosis (nfκb, bcl-2, caspase-3, caspase-8) in the ovary differed among the three groups. The nrf2-bcl2 pathways were also positively correlated with GSI. The pathogenic changes were linked to chronic hypoxia, according to the results of the PCA, and the negative consequences were more severe for the fish in the HG (DO 2.0 mg/L) than for those in the NG and LG. Together, our results show that apoptosis and the antioxidant system are dysregulated under chronic hypoxia stress, and this may be responsible for impaired gonad development in hypoxia-stressed female Nile tilapia.

Protective effect of equol intake on bladder dysfunction in a rat model of bladder outlet obstruction.

This study evaluates the impact of equol, a metabolite of soy isoflavone, on bladder dysfunction in rats with bladder outlet obstruction (BOO). In addition, we investigate its potential as a neuroprotective agent for the obstructed bladder and discuss its applicability in managing overactive bladder (OAB). Eighteen male Sprague-Dawley rats were divided into three groups (six rats per group) during the rearing period. The Sham and C-BOO groups received an equol-free diet, while the E-BOO group received equol supplementation (0.25 g/kg). At 8 weeks old, rats underwent BOO surgery, followed by continuous cystometry after 4 weeks of rearing. The urinary oxidative stress markers (8-hydroxy-2'-deoxyguanosine and malondialdehyde) were measured, and the bladder histology was analyzed using hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining (neurofilament heavy chain for myelinated nerves, peripherin for unmyelinated nerves, and malondialdehyde). Equol reduced BOO-induced smooth muscle layer fibrosis, significantly prolonged the micturition interval (C-BOO: 193 s, E-BOO: 438 s) and increased the micturition volume (C-BOO: 0.54 mL, E-BOO: 1.02 mL) compared to the C-BOO group. Equol inhibited the increase in urinary and bladder tissue malondialdehyde levels. While the C-BOO group exhibited reduced peripherin alone positive nerve fibers within the smooth muscle layer, equol effectively attenuated this decline. Equol reduces lipid peroxidation and smooth muscle layer fibrosis in the bladder and exhibited neuroprotective effects on bladder nerves (peripheral nerves) and prevented the development of bladder dysfunction associated with BOO in rats. Consumption of equol is promising for the prevention of OAB associated with BOO.

Protective role of the ginsenoside Rg1 against methimazole-induced gestational hypothyroidism on reflexive behaviors, conditioned fear and cortical antioxidant levels in mice offspring

Ginsenoside Rg1(Rg1), a monomer of a tetracyclic triterpenoid derivative, possesses diverse medicinal properties attributed to its unique chemical structure and may have beneficial effects on fetal development. This study aimed to investigate the protective effects of prenatal exposure to Rg1 against Methimazole-induced gestational hypothyroidism on reflexive behaviors, conditioned fear, and cortical antioxidant levels in mouse offspring.40 female virgin mice and 12 male NMRI mice were assigned to four groups: group 1 served as the control, group 2 received Methimazole(MMI) at a concentration of 0.02% in their drinking water, group 3 received Rg1(150 mg/kg), and group 4 received both MMI and Rg1.Groups of 2–4 were administered the substances from days 1–9 of gestation. After delivery, pups were selected, and reflexive motor behaviors and conditioned fear were assessed. Additionally, levels of brain tissue catalase(CAT), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione peroxidase(GPx) levels were measured. Furthermore, postpartum immobility time in the forced swimming test (FST), tail suspension test (TST), and the number of squares crossed in the open field test (OFT)were determined. The results demonstrated that maternal exposure to Rg1 improved ambulation score, hind-limb suspension score, grip strength, front-limb suspension, hind-limb foot angle, negative geotaxis, surface righting, and conditioned fear in hypothyroidism-induced offspring(P<0.05). Rg1 decreased immobility time in the FST, and TST, and increased the number of squares crossed in the OFT in postpartum hypothyroidism-induced mice(P<0.05). Moreover, Rg1 reduced brain tissue MDA levels and increased brain tissue CAT, SOD, and GPx levels in mice and their offspring(P<0.05). These findings indicate that Rg1 mitigated postpartum depression in mice and improved reflexive motor behaviors in their pups.

Effects of quercetin on gentamicin-induced experimental testicular injury in rats.

The purpose of this study was to investigate the effects of gentamicin (GEN) on the testis and whether quercetin (QUE) has any protective effect. Twenty-four adult male Sprague-Dawley rats were divided into equal four groups: control (0.9% saline solution), GEN (80 mg∕kg GEN), QUE (50 mg∕kg QUE) and GEN+QUE (80 mg∕kg GEN + 50 mg∕kg QUE). Histopathological (HP) evaluation of testis was performed, epididymal sperm parameters were analyzed and oxidative status was evaluated. The use of QUE improved the HP findings, such as decrease in the germinal epithelial thickness in the testicular tissue of the GEN group, decrease in the Johnsen's tubular biopsy score (JTBS), increase in the rate of immature cell shedding tubules, and the apoptotic index (AI). In the GEN group, sperm count, and abnormal morphology increased compared to the control group; the viability and motility decreased according to the sperm analysis results. In the GEN+QUE group, QUE was found to improve sperm viability and morphology. In the GEN group, tissue malondialdehyde (MDA) levels increased while superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels decreased. Compared with the GEN+QUE group, it was found that the tissue MDA level decreased, while the levels of SOD, CAT and GPx increased. The results demonstrate that GEN impairs testicular structure and function, and QUE treatment can prevent this adverse effect.

Antiarthritic potential of ethanolic extract of Ixora coccinea leaves on complete Freund's adjuvant-induced arthritis in animal model.

Ixora coccinea leaves possess antioxidant, anti-inflammatory, antinociceptive, antimutagenic, and gastroprotective properties. On this background, its antiarthritic potential was evaluated. The objective is to evaluate the effect of Ethanolic extract of Ixora coccinea leaves (EEICL) on complete Freund's adjuvant-induced arthritis in rats. PG research laboratory, Pharmacology Department, MKCG Medical College, Berhampur, Odisha. Thirty-six Wistar albino rats were randomly distributed into sixgroups (n = 6) as follows: Gr 1 (normal control)-DW p.o, Gr-2 (disease control [DC] - Tween 80 p.o), Gr-3 (piroxicam 0.9 mg/kg p.o), Gr-4 (EEICL-1 g/kg, p.o, Gr 4-EEICL-1.5 g/kg p.o, Gr 5-ED50 (0.82 g/kg) + piroxicam (0.45 mg/kg) p.o. After induction of arthritis, drugs, and vehicles were administered daily from 5th to 25th day. On 0, 5th, 10th, 15th, and 25th day, parameters like body weight, rotarod fall time, paw volume displacement, and arthritis index were measured. On the last day, Erythrocyte sedimentation rate (ESR), tissue malondialdehyde (MDA), and histopathological analysis were done. Analysis of parametric data was done by one-way ANOVA and nonparametric data by Kruskal-Wallis test using graph pad prism 7.0. P < 0.05 was considered statistically significant. EEICL (1.5 mg/kg) showed anti-arthritic effect compared with DC. Rotarod fall-off time 137.5 ± 2.5 sec and body weight (139 ± 12.74 g) were increased significantly. The percentage inhibition of paw volume was increased(52%) whereas arthritic score(0.33), ESR(3.51mm/hr), synovial tissue MDA level (0.62±0.13µmol/gm) and Mankin score(2) were reduced significantly as compared to disease control. EEICL has anti-arthritic potential in rat model.

Unveiling of the antileishmanial activities of Linalool loaded zinc oxide nanocomposite through its potent antioxidant and immunomodulatory effects

This study aimed to produce linalool loaded zinc oxide nanocomposite (LZNPs) and assess its in vitro and in vivo antileishmanial effects against Leishmania major. LZNPs was produced through the synthesis of an ethanolic solution containing polyvinyl alcohol. The average size of LZNPs was determined to be 105 nm. The findings indicated that LZNPs displayed significant (p < 0.01) antileishmanial effects on promastigotes and amastigotes. Following exposure of promastigotes to LZNPs, there was a notable rise in the percentage of early and late apoptotic cells from 9.0 to 57.2 %. The gene expression levels of iNOS, IFN-γ, and TNF-α in macrophages were upregulated in a dose-dependent approach following exposure to LZNPs. LZNPs alone and in conjunction with glucantime (Glu) resulted in a reduction in the diameter and parasite load of CL lesions in infected mice. Treatment of the CL-infected mice with LZNPs at 25 and 50 mg/kg mainly in combination with Glu-reduced the tissue level of malondialdehyde (MDA), increased both gene and protein expression of the antioxidant enzymes as well as raised the expression level of IFN-γ and IL-12 cytokines, whereas caused a significant reduction in the expression level of IL-4. The present study shows that LZNPs has potent antileishmanial effects and controls CL in a mice model through its antioxidant and immunomodulatory properties. Further investigation, especially in clinical trials, could explore the potential use of this nanocomposite in managing and treating CL.

Effect of three different insect larvae on growth performance and antioxidant activity of thigh, breast, and liver tissues of chickens reared under mild heat stress

This study investigated the potential of insect-based diets to mitigate heat stress impact on broiler chickens, focusing on growth performance and antioxidant stability. Four dietary groups were examined, including a control and three treated groups with Tenebrio molitor (TM), Hermetia illucens (HI), and Zophobas morio (ZM) larvae, respectively, at a 5% replacement ratio. Temperature and relative humidity of the poultry house were monitored. Under heat stress conditions, the HI-fed group consistently exhibited the highest body weight, demonstrating their remarkable growth-promoting potential. TM-fed broilers also displayed commendable growth compared to the control. Insect larvae inclusion in the diet improved feed intake during early growth stages, indicating their positive influence on nutrient utilization. Regarding antioxidant stability, malondialdehyde (MDA) levels in the liver, an oxidative stress and lipid peroxidation marker, were significantly lower in the TM-fed group, suggesting reduced oxidative stress. While the specific insect-based diet did not significantly affect MDA levels in thigh and breast tissues, variations in the total phenolic content (TPC) were observed across tissues, with HI larvae significantly increasing it in the breast. However, the total antioxidant capacity (TAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) levels did not differ significantly among dietary groups in the examined tissues. Results suggest that insect-based diets enhance broiler growth and potentially reduce oxidative stress, particularly in the liver. Dietary presence of bioactive compounds may contribute to these benefits. Further research is required to fully elucidate the mechanisms underlying these findings. Insect-based diets seem to offer promise as feed additives in addressing the multifaceted challenges of oxidative stress and enhancing broiler health and resilience under heat stress conditions.

Tomato Extract Antagonizes Cadmium-Induced Hepatotoxicity and Nephrotoxicity in Mice and HepG2 Cells: Inhibition of Oxidative Damage and Apoptosis

Cadmium (Cd), a highly toxic heavy metal, accumulates in the liver and kidneys in the human body by several routes. Tomatoes and related processed food possess multiple physiological functions such as antioxidation, antiinflammation, and anticancer. Herein, to investigate whether tomato extract (TE) can protect against cadmium chloride (CdCl2)-induced oxidative damage in the liver and kidneys, the oxidative damage models were established in vitro and in vivo, and the control group and TE intervention groups were also set up. A significant elevation was observed in Cd concentration and the level of alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (CR), and uric acid (UA) in the serum of CdCl2-treated rats compared with the control group, by contrast, these values were reduced following TE intervention. Moreover, it was found that exposure to CdCl2 decreased the superoxide dismutase (SOD) activity, glutathione (GSH) level, and catalase (CAT) activity and raised the malondialdehyde (MDA) level in serum, liver tissues, kidney tissues, and HepG2 cells, which can be reversed by TE to mitigate the oxidative damage. In addition, TE exerted an inhibitory effect on cell apoptosis in both liver and kidneys brought on by CdCl2 intoxication, as manifested by the downregulation of Caspase-3 protein and the up-regulation of B-cell lymphoma gene 2 (Bcl-2) protein after TE treatment. Altogether, our study reinforces previous findings that CdCl2 exposure disrupted the redox homeostasis, leading to oxidative damage in both liver and kidneys. More importantly, our findings suggest that the hepatorenal protective effect of TE against CdCl2 toxicity is implicated in the inhibition of oxidative stress and apoptosis.

Investigation of the effects of white tea on liver fibrosis: An experimental animal model.

Liver fibrosis is a common, progressive disease that affects millions of patients worldwide. In this study, it was aimed at investigating the effect of white tea on liver fibrosis in an in-vivo environment by creating an experimental liver fibrosis model on rats. In this study, an experimental liver fibrosis model was created with carbon tetrachloride (CCl4) in Sprague-Dawley rats to investigate the effect of white tea on liver fibrosis. Rats are treated with CCl4 (1 mL/kg) to constitute the liver fibrosis model. White tea was given adlibitum with drinking water. As a result of the study, liver tissue hydroxyproline levels were found to be significantly lower (p = .001) in the white tea group. Histopathologically, it was found that the liver tissue histopathological damage score (LHDS) and fibrosis scoring were significantly lower (p < .001) in the white tea group. However, although it was not statistically significant in the group given white tea, compared with the fibrosis group, it was found that the malondialdehyde (MDA) level in the liver tissues was lower, the glutathione (GSH) level was higher, and the serum alanine aminotransferase (ALT) levels were lower. The study explained the effect of white tea on liver fibrosis and suggested that white tea might be beneficial in reducing the progression of liver fibrosis.

The ameliorating effects of apigenin and chrysin alone and in combination on polycystic ovary syndrome induced by dehydroepiandrosterone in rats

Objective: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age and is one of the main causes of ovulation infertility, affecting 5-10% of women. Inflammation, hormonal imbalances, and disruption of the oxidant-antioxidant balance are the main factors in the pathophysiology of PCOS. This study was designed to answer the question of whether apigenin and chrysin have therapeutic effects on the dehydroepiandrosterone (DHEA)-induced rat model of PCOS. Materials and Methods: The experimental PCOS model was created by administering 6 mg/100g dehydroepiandrosterone (DHEA) subcutaneously to 21-day-old female Wistar rats for 28 days, followed by treatment with natural agents 50 mg/kg apigenin and 50 mg/ kg chrysin by oral gavage twice a week for one month. The predominant cell type was determined by microscopic analysis in vaginal smears daily from day 10 to day 28 of the experiment. In tissue supernatants, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and malondialdehyde (MDA) levels were obtained by spectrophotometric method with appropriate manual methods; follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, interleukin (IL)-18, IL-1β, and IL- 13 levels were determined by enzyme-linked immunosorbent assay (ELISA) method. In addition, histological sections obtained from ovarian tissue samples were stained with hematoxylin-eosin and examined under a light microscope. Results: The results showed that treatment with apigenin and chrysin alone and in combination reduced MDA, LH, FSH, progesterone, IL-1β, IL-13, and IL-18 levels compared with PCOS rats. Furthermore, enzymatic activities of antioxidants including CAT, SOD, and GPx in the ovaries increased in therapeutic groups according to the PCOS group. Conclusion: In conclusion, this study demonstrates the potential therapeutic efficacy of apigenin and chrysin, either alone or in combination, in alleviating the hormonal imbalances, inflammation, and oxidative stress in DHEA-induced PCOS rats. Apigenin, in particular, emerges as a promising agent for PCOS treatment, showing superiority over chrysin and combination treatments in ameliorating cystic follicles and improving various parameters associated with PCOS pathophysiology. These findings suggest that apigenin holds promise as a novel therapeutic agent for PCOS and warrants further investigation in clinical settings.

Metabolomic modelling and neuroprotective effects of carvacrol against acrylamide toxicity in rat's brain and sciatic nerve.

The study aimed to investigate the harmful effects of acrylamide (AA), which forms in carbohydrate-rich foods at temperatures above 120°C, on the central and peripheral nervous systems and to evaluate the potential neuroprotective effects of carvacrol (CRV). Male Wistar Albino rats were subjected to AA (40 mg/kg/bw/day) and CRV (50 mg/kg/bw/day) for 15 days. Following the last administration, evaluations revealed disrupted gait, heightened thermal sensitivity and altered paw withdrawal thresholds in AA-exposed rats. Notably, AA reduced glutathione (GSH) and raised malondialdehyde (MDA) levels in both brain and sciatic nerve tissues. AA raised nuclear factor erythroid 2-related factor 2 (Nrf2), caspase 3 and nuclear factor κB (NF-κB) gene expressions while decreasing NR4A2. CRV co-administration mitigated gait abnormalities, elevated GSH levels and lowered MDA levels in both tissues. CRV also modulated gene expression, reducing Nrf2 and NF-κB while increasing NR4A2. Histopathological signs of AA-induced neurodegeneration and elevated glial fibrillary acidic protein levels observed in brain and sciatic nerve tissues were rectified with simultaneous administration of CRV, thereby demonstrating neuroprotective efficacy in both regions. This study is pioneering in demonstrating CRV's neuroprotective potential against AA-induced neurotoxicity in both central and peripheral nervous systems, effectively addressing limitations in the literature. In conclusion, the study revealed AA-induced neurodegeneration in the brain and sciatic nerve, with CRV significantly mitigating this neurotoxicity. This novel research underscores CRV's promise as a neuroprotective agent against AA-induced adverse effects in both the central and peripheral nervous systems.

Effects of benidipine, paracetamol, and their combination on postoperative and normal tissue pain thresholds.

Introduction: In clinical practice, inadequate pain inhibition leads to increased morbidity and mortality. Increased intracellular calcium, oxidants, and proinflammatory cytokines are known to play a role in the pathogenesis of postoperative pain. Therefore, we investigated the analgesic effects of benidipine, paracetamol, and benidipine-paracetamol combination (BPC) on postoperative and normal pain thresholds in rats. Material and methods: Sixty-four male albino Wistar rats weighing 285-295g were used. The without-incision rats were divided into 4 subgroups: healthy control, benidipine alone, paracetamol alone, and BPC. The scalpel-incision rats were divided into 4 subgroups: scalpel incision, scalpel incision + benidipine, scalpel incision + paracetamol, and scalpel incision + BPC. Paw pain thresholds of rats were measured using a Basile algesimeter. Biochemical analyses were performed on the paw tissues of 6 rats randomly taken from the experimental groups, each containing 8 rats. Rats were sacrificed immediately after the measurements. After the pain threshold tests were finished, the paw tissues were removed and malondialdehyde (MDA), total glutathione (tGSH), cyclooxygenase (COX), and interleukin-6 (IL-6) levels were measured. Results: There was no significant difference between the groups in paw pain threshold and measured biochemical parameters in rats without incision. The decrease in the pain threshold of the incised paw was also best prevented by BPC, followed by benidipine and then paracetamol. Furthermore, increases in scalpel-incised paw tissue MDA, COX-2, and IL-6 levels and the decrease in tGSH were significantly suppressed by benidipine and BPC, while paracetamol could only significantly inhibit the increase in IL-6 production. Conclusion: The combination of the L-type Ca2+ channel blocker benidipine and paracetamol (BPC) may provide potent analgesia. Our experimental results support that BPC may be useful in the treatment of severe pain that cannot be adequately inhibited by paracetamol.

Investigation of the Subchronic Toxicity of Graded Doses of Extracts of Dialium guineense Stem Bark in Rats

Aim: To investigate the subchronic toxicity of graded doses of aqueous and ethanol extracts of D. guineense stem bark in rats. Materials and Methods: A total of seventy (70) rats (35 per extract) weighing 160 to 180 g (mean weight = 170 ± 10 g) were divided into seven (7) groups of five (5) rats each. Group I served as control, while rats in groups II – VII received graded doses of extract (200 – 5000 mg/kg body weight, bwt) for a duration of 28 days. Weight parameters, liver malondialdehyde (MDA) level and histopathological assessment were carried out. Results: Percentage increases in body weights of rats treated with aqueous or ethanol extract of D. guineense stem bark were significantly reduced, when compared with control group (p &lt; 0.05), but there were no significant differences in the corresponding relative organ weights and tissue MDA level, among the groups (p &gt; 0.05). Similarly, the extracts did not significantly alter the normal architecture of the liver, but induced mild periportal lymphocytosis and kupffer cell activation. Conclusion: The aqueous and ethanol extracts of the medicinal plant stem bark did not elicit any deleterious effects on rat liver.

Effect of sugammadex, rocuronium and sevoflurane on oxidative stress and apoptosis in cerebral ischemia reperfusion model in rats.

Cerebral ischemia-reperfusion (I/R) injury causes neurological dysfunction and cell death. Sugammadex, as a large molecule, is normally difficult to pass through the blood-brain barrier (BBB). In ischemia, molecules can pass into the brain tissue. In this study, we aimed to evaluate the effect of sugammadex in the presence of cerebral I/R damage in rats with a general anesthesia model with sevoflurane and rocuronium. Rats were divided into 7 groups; Group 1 (Control), Group 2 (Sham), Group 3 (Sevoflurane), Group 4 (Sugammadex), Group 5 (Sevoflurane + Rocuronium), Group 6 (Sevoflurane + Sugammadex), Group 7 (Sevoflurane + Rocuronium + Sugammadex). Brain tissues of rats with cerebral I/R damage with bilateral carotid occlusion were removed. Tissue Malondialdehyde (MDA), Myeloperoxidase (MPO), and Superoxide dismutase (SOD) levels were examined with ELISA and apoptosis was examined by Caspase-3. The number of caspase-3 positive cells decreased the most in Group 4 compared to the other groups. Group 4's mean MDA and MPO levels were lower than Group 2. There was no significant difference in terms of SOD levels. The apoptotic effect of sugammadex was lowest compared to other agent groups, and it did not increase oxidative damage as much as the other groups.

Ameliorative effects of androstenediol against acetic acid-induced colitis in male wistar rats via inhibiting TLR4-mediated PI3K/Akt and NF-κB pathways through estrogen receptor β activation

5-androstenediol (ADIOL) functions as a selective estrogen receptor β (ERβ) ligand with a protective effect against many diseases. So, we conducted a novel insight into its role in acetic acid (AA)-induced colitis and investigated its effect on TLR4-Mediated PI3K/Akt and NF-κB Pathways and the potential role of ERβ as contributing mechanisms. Methods: Rats were randomized into 5 Groups; Control, Colitis, Colitis + mesalazine (MLZ), Colitis + ADIOL, and Colitis + ADIOL + PHTPP (ER-β antagonist). The colitis was induced through a rectal enema of acetic acid (AA) on the 8th day. At the end of treatment, colons were collected for macroscopic assessment. Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor kappa b (NF-κB), toll-like receptor (TLR4), and phosphorylated Protein kinase B (pAKT) were measured. Besides, Gene expression of interleukin-1beta (IL-1β), metalloproteases 9 (Mmp9), inositol 3 phosphate kinase (PI3K), Neutrophil gelatinase-associated lipocalin (NGAL), ERβ and NLRP6 were assessed. Histopathological and immunohistochemical studies were also investigated. Results: Compared to the untreated AA group, the disease activity index (DAI) and macroscopic assessment indicators significantly decreased with ADIOL injections. Indeed, ADIOL significantly decreased colonic tissue levels of MDA, TLR4, pAKT, and NF-κB immunostainig while increased SOD activity and β catenin immunostainig. ADIOL mitigated the high genetic expressions of IL1β, NGAL, MMP9, and PI3K while increased ERβ and NLRP6 gene expression. Also, the pathological changes detected in AA groups were markedly ameliorated with ADIOL. The specific ERβ antagonist, PHTPP, largely diminished these protective effects of ADIOL. Conclusion: ADIOL could be beneficial against AA-induced colitis mostly through activating ERβ.

Amlodipine alleviates renal ischemia/reperfusion injury in rats through Nrf2/Sestrin2/PGC-1α/TFAM Pathway

BackgroundPreviously, observational studies showed that amlodipine can mitigate calcineurin inhibitor- and contrast-induced acute kidney injury (AKI). Herein, we aimed to measure the effect of amlodipine on renal ischemia/reperfusion (I/R) injury and find the underlying mechanisms.Materials and methodsBilateral renal I/R was induced by clamping the hilum of both kidneys for 30 min. The first dose of amlodipine 10 mg/kg was gavaged before anesthesia. The second dose of amlodipine was administered 24 h after the first dose. Forty-eight hours after I/R, rats were anesthetized, and their blood and tissue specimens were collected.ResultsAmlodipine significantly decreased the elevated serum levels of creatinine and blood urea nitrogen (BUN) and mitigated tissue damage in hematoxylin & eosin (H&E) staining. Amlodipine strongly reduced the tissue levels of malondialdehyde (MDA), interleukin 1β (IL1β), and tumor necrosis factor α (TNF-α). Amlodipine enhanced antioxidant defense by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2. Furthermore, amlodipine significantly improved mitochondrial biogenesis by promoting Sestrin2/peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway. It also enhanced autophagy and attenuated apoptosis, evidenced by increased LC3-II/LC3-I and bcl2/bax ratios after renal I/R.ConclusionThese findings suggest that amlodipine protects against renal I/R through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.

Nephroprotective Effect of Vinpocetine against Vancomycin-induced Nephrotoxicity in Rats

Background: The kidney is a vital organ for the body and is vulnerable to drug toxicity. For methicillin-resistant Staphylococcus aureus, vancomycin is the antibiotic of choice. It has been accompanied by nephrotoxicity, which restricts its use. Numerous studies have reported that nephrotoxicity was linked to oxidative stress and inflammatory response. Vinpocetine is a derivative of vincamine alkaloid used to treat some neurological disorders and has antioxidant and anti-inflammatory effects. The objective of the study: To evaluate the nephroprotective effect of vinpocetine against vancomycin-induced nephrotoxicity in rats. Methods: Twenty-four albino male rats were randomly selected and divided into three groups (n = 8): (1) Normal group: apparently healthy rats. (2) Induction group: treated with vancomycin (200mg/kg) twice daily intraperitoneally for 14 days. (3) Vinpocetine group: As the group (2) and treated with vinpocetine (2.5mg/kg) twice daily orally, an hour before vancomycin administration. Results: Vinpocetine group demonstrated a significant decrease in urea, creatinine, and cystatin C serum levels compared to the induction group. Also, it showed a significant reduction in the renal tissue level of malondialdehyde and a significant elevation in the renal tissue level of glutathione as compared to the induction group. Furthermore, the vinpocetine group showed a significant decrease in the renal tissue levels of tumour necrosis factor-alpha and neutrophil gelatinase-associated lipocalin. Histologically, all rats in vinpocetine group showed a significantly reduced level of renal tissue damage. Conclusion: The present study shows that vinpocetine exhibited nephroprotective due to its antioxidant and anti-inflammatory effects. Keywords: Nephrotoxicity, Oxidative stress, Vancomycin, Vinpocetine.