Tissue Oxidative Stress Parameters Research Articles

Etilen Glikolla İndüklenmiş Nefrolitiyazisli Sıçan Böbrekleri Üzerinde Viburnum Opulus L’nin Etkileri

Objective: Recent research has centered on the role of oxidative stress and free oxygen radicals in the formation of stones. Viburnum opulus L. (VO) is a fruit species known for its antioxidant activity, and its juice preparation is used in Turkish traditional medicine for stone removal. This study aimed to investigate the effects of VO on calcium oxalate (CaOx) crystallization and oxidative stress in rats with ethylene glycol (EG)-induced nephrolithiasis. Material and Methods: Fifty adult male Wistar Hannover rats were divided into five groups: control (Group 1), EG (Group 2), EG + 50 mg/kg VO (Group 3), EG + 100 mg/kg VO (Group 4), and EG + 200 mg/kg VO (Group 5). On days 7, 14, and 28, 24-hour urine was collected, and blood samples were taken. On day 28, the rats were sacrificed, and inflammation, oxidative stress, and CaOx crystallization in kidney tissue were evaluated under polarized light microscopy. Results: A statistically significant difference was found between Group 1 and Group 2 in terms of serum inflammation parameters, acute kidney injury, and oxidative stress evaluated on days 7, 14, and 28, and tissue inflammation and oxidative stress parameters evaluated on day 28. It was observed that these parameters improved in Groups 3-5 compared to Group 2, and the level of statistical significance increased as the dose increased. In the histopathological evaluation of the tissues on day 28, the mean number of crystals was statistically significantly higher in Group 2 than in Group 1. These parameters improved in Groups 3-5 compared to Group 2, and there was a statistically significant difference when Groups 4 and 5 were compared to Group 2. Conclusion: It was found that VO improved inflammation, oxidative stress, acute kidney injury, and CaOx crystallization in rats with EG-induced nephrolithiasis in direct proportion to the increase in dose.

TLR4/ MyD88/NF-κB signaling pathway involved in the protective effect of diacerein against lung fibrosis in rats.

Pulmonary fibrosis (PF) is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on PF injury has not yet been fully clarified. Therefore, the current study aimed to detect its protective effect on lung tissue with the explanation of possible underlying mechanisms. Adult male albino rats were assigned to four groups: control group, diacerein control group, PF non-treated group, and PF diacerein pretreated group. Lung tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and myeloid differentiation factor 88 (MyD88) levels were determined. Histopathological examination of lung tissue and immunohistochemical studies of nuclear factor-kappa B (NF-κB), and transforming growth factor- β (TGF-β) were also done. Diacerein pretreatment has the ability to restore the PF damaging effect, proved by the reduction of the oxidative stress and lung tissue inflammation via downregulation of TLR4/NF-κB signaling pathway together with the restoration of TGF-β level and improvement of the histopathological and immunohistochemical study findings in the lung tissue. These results suggested the protective effect of diacerein on PF relies on its antioxidant and anti-inflammatory effects reducing TLR4/NF-κB signaling pathway.

Terminalia catappa fruit extract effect on biochemical parameters of the brain like oxidative stress, amyloid beta and Acetylcholinesterase

AbstractBackgroundThe present research deals with the assessment of Anti‐Alzheimer affect Terminalia catappa fruit extracts (TCFE) in Alzheimer diseased (AD) rat and also propose its probable mechanism of action.MethodAlzheimer disease was induced by administering streptozotocin i.e. STZ (3 mg/kg) by Intracerebroventricular injection (i.c.v. injection) day 1st and 3rd day, after surgery. Stereotaxic apparatus was used for surgery. Anesthetized rats were used for surgery. Streptozotocin induced Alzheimer diseased rats were treated with hydroalcoholic extract of TCFE (100 and 200 mg/kg, p.o.) for 14 days. Effects of TCFE in Alzheimer diseased rats were assessed for biochemical parameter in the brain tissue oxidative stress parameters (SOD, CAT, GSH and TBARS), amyloid β peptide (Aβ) and acetylcholinesterase (AchE)ResultTCFE significantly (p<0.01) decreases the Aβ1‐40, Aβ1‐42 peptides. Acetylcholinesterase level in the rats brain tissue reduced compared to Alzheimer diseased rats. TCFE significantly decreases the oxidative stress level in Alzheimer diseased rats.ConclusionEffect of TCFE on superoxide dismutase, catalase, reduced glutathione and Thiobarbituaric acid reactive species in the brain tissue of STZ treated AD rats were shown in Table 1.TCFE significantly increased level of antioxidants in brain tissues ((P< 0.01)). β amyloid level of Aβ1‐40 and Aβ1‐42 in the brain tissue decreased significantly (p<0.01) in TCFE treated group compared to AD rats (Negative control group)(Table 2) STZ administration produced significant elevation in brain AchE activity compared to control group of rats. However, TCFE significantly inhibited (P< 0.01) of AchE activity in brain tissue as compared with the negative control group of rats.

Short-term trivalent arsenic and hexavalent chromium exposures induce gut dysbiosis and transcriptional alteration in adipose tissue of mice.

Inorganic arsenic [As(III)] and hexavalent chromium [Cr(VI)] can potentially affect metabolic functions. These heavy metal(s)/metalloids can also affect the gut microbial architecture which affects metabolic health. Here, we assessed the effects of short-term exposure of As(III) and Cr(VI) on key transcription factors in adipose tissues and on selected gut microbial abundances to understand the possible modulatory role of these toxicants on host metabolic health. qRT-PCR based relative bacterial abundance studies in cecal samples, gene expression analysis for gut wall integrity in ileum and colon and adipogenesis, lipolysis, and thermogenic genes in gonadal white and brown adipose tissue (gWAT and BAT), along with tissue oxidative stress parameters have been performed. As(III) and Cr(VI) exposure reduced beneficial Lactobacilli, Bifidobacteria, Akkermansia, Lachenospiraceae, Fecalibacterium, Eubacterium, and clostridium coccoid group while increasing lipopolysaccharides producing Enterobacteriaceae abundances. It also impaired structural features and expression of key tight junction and mucin production genes in ileum and colon (Cld-2, Cld-4, ZO-1, ZO-2, MUC-2 and - 4). In gWAT it inhibited adipogenesis (PPARγ, FASN, SREBP1a), lipolysis (HSL, ACOX-1), and thermogenesis (UCP-1, PGC1a, PRDM-16, PPARa) related genes expression, whereas in BAT, it enhanced adipogenesis and reduced thermogenesis. These exposures also reduces the endogenous antioxidants levels in these tissues and promote pro-inflammatory cytokines genes expression (TLRs, IL-6, MCP-1). The combinatorial exposure appears to have more deleterious effects. These effects of As(III) and Cr(VI) may not directly be linked to their known toxicological effects, instead, more intriguing crosstalk with gut microbial ecosystem hold the key.

Phoenix Dactylifera L. Tree Fruit Exerts Cardioprotective Effect Against DoxorubicinInduced Heart Damage in Rats via Inhibition of Oxidative Stress

Introduction: Phoenix Dactylifera L (PDL) is a fruit containing a rich source of nutrients and bioactive molecules. Doxorubicin is a widely used agent, especially in the treatment of solid cancers. However, cardiotoxicity is one of its most challenging side effects. The present study aimed to investigate the preventive effect of PDL extract against doxorubicin-induced cardiotoxicity. Patients and Methods: A total of 24 albino Wistar rats were divided into four equal groups. Phoenix Dactylifera L (PDLG) and Phoenix Dactylifera L + doxorubicin (PDXG) groups were strictly fed PDL for two weeks. The control group (CG) and the doxorubicin group (DOXG) were fed a standard diet. During this time, 5 mg/kg of doxorubicin was injected intraperitoneally to DOXG and PDXG once a day. Results: Administration of doxorubicin to the DOXG significantly increased tissue oxidative stress parameters and caused the cardiac biomarker troponin-I (TP-I) to be released into the circulation; on the contrary, the levels of potent antioxidants such as total glutathione, superoxide dismutase, and catalase significantly decreased in DOXG compared to the other three groups. However, feeding purely with PDL decreased oxidative stress parameters and TP-I levels in PDXG animals, despite exposure to doxorubicin. Additionally, an excessive decrease of tissue antioxidants was prevented when compared to the DOXG. Histopathological damage signs, such as necrosis and hemorrhage, were severe in the DOXG. However, in the PDXG animals, feeding with PDL provided the integrity of the heart tissue structure. Conclusion: PDL was able to improve the cardiotoxic consequences of doxorubicin biochemically and histopathologically, possibly due to its antioxidant properties.

Melatonin ameliorates chronic copper-induced lung injury.

Copper (Cu) is an important trace element required for several biological processes. The use of copper is increasing gradually in several applications. Previous studies suggest that excess levels of copper are attributed to induce oxidative stress and inflammation, mediating tissue damage. Inline, melatonin the hormone of darkness has been reported to exhibit various therapeutic effects including strong free radical scavenging properties and anti-inflammatory effects. However, its effects against pulmonary injury promoted by copper are not explored and remain unclear so far. Therefore, the present study was aimed to investigate the protective effect of melatonin against copper-induced lung damage. Female Sprague Dawley (SD) rats were exposed to 250 ppm of copper in drinking water for 16 weeks and treated with melatonin (i.p.) 5 and 10 mg/kg from the week (13–16th). The extent of tissue damage was assessed by tissue oxidative stress parameters, metal estimation and histological analysis. Copper-challenged rats showed altered oxidative stress variables. In addition, metal analysis revealed increased copper accumulation in the lungs and histological staining results further indicated severe tissue injury and inflammatory cell infiltration in copper-exposed rats. To this side, treatment with melatonin showed antioxidant and anti-inflammatory activities evidenced by reduced oxidative stress, tissue inflammation and collagen deposition as compared to copper-exposed animals. Moreover, spectral findings suggested melatonin treatment modulated the frequency sift, as compared to copper-challenged animals. Altogether, the present results suggest that melatonin might play a potential role in preventing copper-induced lung aberrations via inhibiting the ROS-mediated oxidative stress and inflammation.

Effect of Cerium Oxide on Kidney and Lung Tissue in Rats with Testicular Torsion/Detorsion.

Introduction Testicular torsion is a surgical emergency that results in testicular ischemia as a result of rotation of the spermatic cord around itself. Oxidative damage occurs in the testis and distant organs with the overproduction of free radicals and overexpression of proinflammatory cytokines by reperfusion after surgery. In this study, we aimed to investigate the effects of cerium oxide (CeO2), an antioxidant nanoparticle, on lung and kidney tissues in testicular torsion/detorsion (T/D) in rats. Materials and Methods After ethics committee approval, 24 rats were equally (randomly) divided into 4 groups. Left inguinoscrotal incision was performed in the control (C) group. In group CeO2, 0.5 mg/kg CeO2 was given intraperitoneally 30 minutes before inguinoscrotal incision. In group T/D, unilateral testicular T/D was achieved by performing an inguinoscrotal incision and rotating the left testis 720° clockwise, remaining ischemic for 120 minutes, followed by 120 minutes of reperfusion. In group CeO2-T/D, 0.5 mg/kg CeO2 was given intraperitoneally 30 minutes before testicular T/D. At the end of the experiment, lung and kidney tissues were removed for histopathological and biochemical examinations. Results Glomerular vacuolization (GV), tubular dilatation (TD), tubular cell degeneration and necrosis (TCDN), leukocyte infiltration (LI), and tubular cell spillage (TCS) in renal tissue were significantly different between groups (p = 0.012, p = 0.049, p < 0.003, p = 0.046, and p = 0.049, respectively). GV and TCDN were significantly decreased in group CeO2-T/D compared to group T/D (p = 0.042 and p = 0.029, respectively). Lung tissue neutrophil infiltration, alveolar thickening, and total lung injury score (TLIS) were significantly different between groups (p = 0.006, p = 0.001, and p = 0.002, respectively). Neutrophil infiltration and TLIS were significantly decreased in group CeO2-T/D compared to group T/D (p = 0.013 and p = 0.033, respectively). Lung and kidney tissue oxidative stress parameters were significantly different between groups (p < 0.05). Renal tissue glutathione-s-transferase (GST), catalase (CAT), and paraoxonase (PON) activities were significantly higher, and malondialdehyde (MDA) levels were significantly lower in group CeO2-T/D than in group T/D (p = 0.049, p = 0.012, p < 0.001, and p = 0.004, respectively). GST and PON activities were higher, and MDA levels were lower in group CeO2-T/D than in group T/D in the lung tissue (p = 0.002, p < 0.001, and p = 0.008, respectively). Discussion. In our study, cerium oxide was shown to reduce histopathological and oxidative damage in the lung and kidney tissue in a rat testis torsion/detorsion model.

Curcumin nanoliposomes mitigate wound tissue inflammatory response caused by tooth extraction

Curcumin is a plant-derived compound with polypharmacological properties that are hampered by its poor solubility, fast degradation, etc. Wound closure complications that follow tooth extraction are numerous, and relatively frequently additional treatment is needed to prevent unwanted process chronification. The present study aims to compare the effects of free and the nanoliposome-encapsulated curcumin on tooth extraction wound closure. The experiments were performed on Wistar rats where both forms of curcumin were applied topically on a tooth extraction wound for seven days. Changes in tissue oxidative stress (malondialdehyde and oxidized proteins concentrations, and catalase activity) and inflammation (nitric oxide levels and myeloperoxidase activity) related parameters were studied three and seven days following the tooth extraction. Also, the extent of pathohistological changes and osteopontin immunohistochemical expression were studied. The obtained results indicate that both forms of curcumin prevent an increase in oxidative stress and inflammation-related parameters in the studied samples at 3-and 7-day time points. Additionally, we found that curcumin diminished tissue inflammatory response and osteopontin expression, while at the same time it caused faster granulation tissue maturation. The encapsulation of curcumin in nanoliposomes proved to be better in improving the extraction wound healing process than the free curcumin, giving this formulation a potential in the pharmaceutical industry.

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.

The Hepatoprotective Role of Balanites aegyptiaca Extract and its Nano-Formulation Against Methomyl-Induced Toxicity and Oxidative Stress in Mice via Overexpression of Nrf2

IntroductionMethomyl (MET) is a monomethyl carbamate insecticide that is widely used around the world. MET is highly toxic to humans via oral exposure and mainly affects the liver tissue. It actually induces toxicity through overproduction of Reactive Oxygen Species (ROS) leading to oxidative stress with subsequent destruction of lipids, proteins, and nucleic acids.Materials and MethodsVarious plant extracts have been primarily screened for their antioxidant activities by measuring the free radical scavenging ability. Later, the plant extract with the highest antioxidant efficacy has been further formulated into a nanosuspension and the antioxidative effect has also been investigated against MET. Additionally, liver, kidney, and heart function biomarkers, liver tissue oxidative stress parameters, and total antioxidant capacity were assessed. Moreover, RT-PCR was applied to measure the Nrf2 expression.ResultsThe antioxidant screening data showed that balanites extract (BLT, Balanites aegyptiaca) had the most potent antioxidant activity. Besides, BLT showed dose-dependent improvement in liver, heart, and kidney functions in experimental mice treated with MET. The antioxidant biomarkers in liver tissue and total antioxidant capacity were elevated as compared to the MET-treated group. Furthermore, BLT significantly ameliorated MET-induced toxicity via the induction of Nrf2 and MET hepatic clearance. This study suggests the potential use of BLT extract as a natural antioxidant for the safe management of MET-induced hepatotoxicity and oxidative stress.ConclusionsBased on the presented data in this study, it can be concluded that BLT or BLT-NS can be used as a safe drug for methomyl toxicity.

Protective effects of sinapic acid against cyclophosphamide-induced testicular toxicity via inhibiting oxidative stress, caspase-3 and NF-kB activity in BALB/c mice.

Cyclophosphamide (CP), as a chemotherapeutic agent, with the generation of oxidative stress leads to testicular toxicity. Sinapic acid (SA), as a phenylpropanoid compound has therapeutic activities. This research was planned to evaluate the improving effects of SA versus testicular injury induced by CP. Forty-eight mice were distributed into six groups: untreated, SA (5 and 10mg/kg), CP (200mg/kg) and CP+SA (5 and 10mg/kg). SA was administrated for 7successive days and CP was administered intraperitoneally on the 3rd day of study. On the 10th day of research, testicular toxicity was evaluated by sperm parameters test, tissue (oxidative stress parameters) and serum (testosterone) biochemical, histopathological, and immunohistochemical (Caspase-3 and NF-kB) assays. The findings illustrated that CP induces atypical appearance in tissue structure, disorder of sperm parameters dysfunction, decrease of testosterone, oxidative stress (an increase of MDA and decrease of GSH), apoptosis and inflammation in testicular tissue. SA administration protected testis from oxidative stress and improves testosterone level and structure. Moreover, immunohistochemical findings also showed that SA can inhibit Caspase-3 and NF-kB activity. Data have confirmed that SA could protect testis structure and its functions against CP-induced injury through antioxidant, anti-inflammatory and anti-apoptotic activities.

Determining the effects of Hyperoside as a protective agent against to testicular damage

Aim: The aim of this study is to evaluate the possible beneficial effects of hyperoside (HYP) in the mitigation of torsion detorsion (TD)-induced testicular oxidative damage. Materials and Methods: For this purpose, Wistar Albino rats were grouped (n=6 in each group) as sham, TD and TD+HYP groups. HYP was administered at 50 mg/kg dose p.o for 1 week. Torsion was created by twisting the spermatic cord clockwise by 720 degrees. The detorsion model was made by restoring the spermatic cord. Tissue oxidative and antioxidative stress parameters were measured according to biochemical methods to evaluate oxidative damage in testis. Results: In particular, the oxidative stress parameters we measured were found to be significantly increased compared to the sham group in TD group depending on the TD model, but showed a significant decrease depending on the HYP treatment (p0.05). In addition, it was observed that the antioxidative parameters decreased significantly in the TD group, while this decrease effectively changed in the TD+HYP group. Conclusion: Considering the current results, HYP therapy is thought to be useful in alleviating TD-induced oxidative damage in the testicles.

Diacerein protects rats with liver ischemia/reperfusion damage: Down-regulation of TLR4/ NFκ-B signaling pathway

PurposeLiver ischemia-reperfusion (I/R) injury is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on liver I/R injury has not yet been fully clarified. Therefore, the current study aimed to detect its hepatic protective effect with the explanation of possible underlying mechanisms. MethodsAdult male albino rats were assigned to 4 groups: sham group, diacerein pretreated sham group, I/R non-treated group, and I/R diacerein pretreated group. Serum liver enzymes, hepatic tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and liver fatty acid binding protein (L-FABP) levels were determined. Histopathological examination of liver tissues and immunohistochemical studies of heat shock protein 70, nuclear factor-kappa B, and Cluster of Differentiation 68 were also done. ResultsDiacerein pretreatment has the ability to restore the hepatic I/R damaging effect, proved by the reduction of serum liver enzymes, the decrease of the oxidative stress and hepatic inflammation via down-regulation of TLR4/ NFκ-B signaling pathway together with the restoration of L-FABP level and improvement of the histopathological and immunohistochemical study findings in the hepatic tissue. ConclusionThese results suggested the hepatoprotective effect of diacerein relies on its antioxidant and anti-inflammatory effects reducing TLR4/ NFκ-B signaling pathway.

Extraction and Identification of Two Flavonoids in Phlomoides hyoscyamoides as an Endemic Plant of Iran: The Role of Quercetin in the Activation of the Glutathione Peroxidase, the Improvement of the Hydroxyproline and Protein Oxidation in Bile Duct-Ligated Rats.

Cholestatic liver disease, a serious chronic condition that develops progressive hepatic degeneration through free radicals. The present study was designed to extract and identify two flavonoids in Phlomoides hyoscyamoides plant, native to Iran and evaluate the role of quercetin identified on the liver injury among bile ductligated rats. This study was conducted on 25 male Wistar rats within three groups of sham control, mere bile duct-ligated, and bile duct-ligated with quercetin. The bile duct-ligated animals received quercetin at a dose of 50 mg/kg/day for 10 days, followed by biochemical tests, oxidative stress markers, activity of antioxidant enzymes and hematoxylin and eosin staining. Molecular docking was used to explore the interactive behavior of quercetin with glutathione peroxidase. According to analyses of the obtained extract, two main active ingredients of P. hyoscyamoides were rutin and quercetin. Bile duct-ligated group showed a significant liver necrosis, a clear increase in plasma and tissue oxidative stress parameters, and a decrease in glutathione peroxidase activity as compared to sham control group. Quercetin injection in bile duct-ligated rats resulted in significant decrease in hydroxyproline, protein carbonyl and histopathologic indexes and significant increase in glutathione peroxidase activity (P-value≤0.05). Based on the molecular docking, the quercetin was able to regulate the glutathione peroxidase activity. The quercetin acts as an enzyme inducer by renewing the glutathione peroxidase activity and inhibiting the oxidation of proteins and hence decreases the oxidative stress. These results could be a sign of confirming the positive role of quercetin in attenuating the liver damage and degeneration.

Nicotinamide riboside reduces cardiometabolic risk factors and modulates cardiac oxidative stress in obese Wistar rats under caloric restriction

AimsNAD-based therapeutic strategies are encouraged against obesity and heart disease. Our study, therefore, aimed to investigate the effects of nicotinamide riboside (NR), isolated or combined with caloric restriction (CR), both approaches well-known for stimulating NAD levels, on adiposity parameters, cardiometabolic factors and cardiac oxidative stress in rats submitted to cafeteria diet (CAF). Main methodsAfter 42 days of CAF-induced obesity (hypercaloric and ultra-processed foods common to humans), we examined the effects of oral administration of NR (400 mg/kg for 28 days), combined or not with CR (−62% kcal, for 28 days), on anthropometric, metabolic, tissue, and cardiac oxidative stress parameters in obese male Wistar rats. Key findingsIn obese rats, treatment with NR alone mitigated final body weight gain, reduced adiposity (visceral and subcutaneous), improved insulin resistance, and decreased TG/HDL ratio and heart size. In cardiac OS, treatment with NR increased the antioxidant capacity via glutathione peroxidase and catalase enzymes (in rats under CR) as well as reduced the pro-oxidant complex NADPH oxidase (in obese and lean rats). Hyperglycemia, hypertriglyceridemia and elevated levels of TBARS in the heart were state-dependent adverse effects, induced by treatment with NR. SignificanceThis is the first study to report effects of nicotinamide riboside on cardiac oxidative stress in an obesity model. Nicotinamide riboside, a natural dietary compound, presented antiobesity effects and cardiometabolic benefits, in addition to positively modulating oxidative stress in the heart, in a state-dependent manner.

Effect of fish oil and telmisartan on dehydroepiandrosterone-induced polycystic ovarian syndrome in rats: The role of oxidative stress, transforming growth factor beta-1, and nuclear factor kappa B.

Our aim was to explore the effect of telmisartan and/or fish oil on dehydroepiandrosterone (DHEA)‐induced PCOS in rats. Sixty female rats were divided into six equal groups as follows: Control; DHEA‐induced PCOS; DHEA + Telmisartan; DHEA + Fish oil; DHEA + Carboxymethyl cellulose; and DHEA + Telmisartan +Fish oil group. Plasma sex hormones, anthropometric measurements, and the glycemic indices were measured. Tissue oxidative stress parameters and the proinflammatory cytokines were assessed. The ovaries were subjected to histopathological and electron microscopic examination. Telmisartan and/or fish oil induced significant improvement of insulin resistance with amelioration of oxidative stress and inflammation compared to PCOS group. Also, telmisartan and/or fish oil restored the hormonal levels and the anthropometric measurements to the normal values. This was significant with telmisartan/fish oil combination compared to the use of each of these agents alone. In conclusion, this combination may represent a promising hope for amelioration of PCOS.

Hepatoprotective effect of linagliptin against liver fibrosis induced by carbon tetrachloride in mice.

The current study aimed to investigate linagliptin for its potential role in the prevention of liver fibrosis progression. Balb-C mice were randomly allocated into five groups (10 each): (i) control; (ii) mice were injected intraperitoneally with 50 μL carbon tetrachloride (CCl4) in corn oil in a dose of 0.6 μL/g three times per week for four weeks; (iii) linagliptin was administered orally in a daily dose of 10 mg/kg simultaneously with CCl4; (iv) silymarin was administered orally in a daily dose of 200 mg/kg concomitantly with CCl4; and (v) only linagliptin was administered. Hepatic injury was manifested in the CCl4 group by elevation of biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)), and hepatic fibrosis was evident histopathologically by increased METAVIR score and immunostaining expression of alpha-smooth muscle actin (α-SMA), as well as increased liver tissue oxidative stress parameters, transforming growth factor-β1 (TGF-β1), and mammalian target of rapamycin (mTOR). Linagliptin was able to stop the progression of liver fibrosis, evident histopathologically with reduced METAVIR score and α-SMA expression. The possible mechanism may be via suppression of oxidative stress, TGF-β1, and mTOR, which was associated with improvement of serum biochemical parameters ALT and AST. In conclusion, linagliptin might help to protect the liver against persistent injury-related consequences.

Amelioration of Cisplatin-Induced Ototoxicity in Rats by L-arginine: The Role of Nitric Oxide, Transforming Growth Factor Beta 1 and Nrf2/HO-1 Pathway

Background:Cisplatin is an alkylating agent that inhibits DNA replication and interferes with proliferation of cancer cells. However, the major limiting factor for its use is the possible development of adverse effects, including ototoxicity. Up till now, the mechanisms of this ototoxicity remain poorly understood. However, induction of oxidative stress and activation of the inflammatory cascade were suggested as contributing factors. Purpose:The aim of this study was to explore the effect of L-arginine on cisplatin-induced ototoxicity in rats. Methods:Thirty male adult Wistar rats were divided into three equal groups as follows: control group; cisplatin group and cisplatin + L-arginine group. Auditory brainstem response (ABR), tissue oxidative stress parameters, total nitrate/nitrite, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) content, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α) and interleukin 15 (IL-15) were assessed. Also, the cochlear tissues were subjected to histopathological and electron microscopic examination. Results:Administration of L-arginine to cisplatin-treated rats induced significant decrease in the average ABR threshold shifts at all frequencies, tissue TGF-β1, TNF-α and IL-15 associated with significant increase in tissue antioxidant enzymes, total nitrate/nitrite and Nrf2/HO-1 content compared to cisplatin group. Also, pretreatment of cisplatin-injected rats with L-arginine induced significant improvement of the histopathological and electron microscopic picture compared to cisplatin group. Conclusion:L-arginine may serve as a promising therapeutic modality for amelioration of cisplatin-induced ototoxicity.

Role of nitric oxide in mediating the cardioprotective effect of agomelatine against isoproterenol-induced myocardial injury in rats.

Myocardial infarction (M/I) is a common cause of mortality worldwide. Agomelatine (AGO), a potent melatonin receptor agonist, proved to have ananti-inflammatory and antioxidant effect. The present study aimed to explore the cardioprotective effect of AGO on isoproterenol (ISO)-induced myocardial injury in a rat model and determine the role of nitric oxide (NO) in mediating this beneficial effect. Rats were randomly divided into 6 groups and treated for 12days. Group 1, control, received normal saline. Group 2, ISO group, received ISO (100mg/kg, i.p.) in 11th and 12th days. Group 3, positive control group, received atenolol (100mg/kg/day) + ISO. Group 4, AGO-treated group, received AGO (80mg/kg/day) + ISO. Group 5, L-NNA + ISO, received L-NG-nitro arginine (L-NNA) (25mg/kg, orally) + ISO. Group 6, AGO + L-NNA + ISO, co-treated with AGO + ISO + L-NNA. Serum cardiac enzymes and cardiac tissue oxidative stress parameters were assessed along with histopathological evaluation. Gene expression quantification of nuclear factor erythroid 2 (Nrf-2) and heme oxygenase-1 (HO-1) were assessed. Immunoexpression of inducible NO synthase (iNOS) and caspase-3 were evaluated. The outcomes proved that ISO significantly increased serum cardiac enzymes, with histopathological changes of myocardial tissue along with a major increase in oxidative, inflammatory, and nitrosative stress, besides a reduction in cardiac Nrf-2 and HO-1 gene expressions with marked myocardial cell apoptosis. However, pretreatment with AGO significantly reversed these profound ISO myocardial damaging effects. AGO protects against ISO-induced myocardial injury through its antioxidant, anti-inflammatory, and anti-apoptotic effects with modulation of NOS enzymes.

Thirty-day experimental diabetes impairs contractility and increases fatigue resistance in rat diaphragm muscle associated with increased anti-oxidative activity.

Diabetes mellitus is a metabolic disorder that can generate tissue damage through several pathways. Alteration and dysfunction of skeletal muscle are reported including respiratory muscles, which may compromise respiratory parameters in diabetic patients. We have aimed to evaluate the diaphragm muscle contractility, tissue remodeling, oxidative stress, and inflammatory parameters from 30 day streptozotocin-treated rats. The diaphragm contractility was assessed using isolated muscle, tissue remodeling using histology and zymography techniques, and tissue oxidative stress and inflammatory parameters by enzyme activity assay. Our data revealed in the diabetes mellitus group an increase in maximum tetanic force (4.82 ± 0.13 versus 4.24 ± 0.18 N/cm2 (p = 0.015)) and fatigue resistance (139.16 ± 10.78 versus 62.25 ± 4.45 s (p < 0.001)), reduction of 35.4% in muscle trophism (p < 0.001), increase of 32.6% of collagen deposition (p = 0.007), reduction of 21.3% in N-acetylglucosaminidase activity (p < 0.001), and increase of 246.7% of catalase activity (p = 0.002) without changes in reactive oxygen species (p = 0.518) and tissue lipid peroxidation (p = 0.664). All observed changes are attributed to the poor glycemic control (471.20 ± 16.91 versus 80.00 ± 3.42 mg/dL (p < 0.001)), which caused defective tissue regeneration and increased catalase activity as a compensatory mechanism.