Diclofenac (DIC) is a non-steroidal anti-inflammatory drug (NSAID) which is known to induce oxidative stress. Dithiocarbamates are compounds with proven antioxidant effect. The aim of the present study was to investigate the antioxidant capacity of diisopropyldithiocarbamates sodium salt (a synthetized compound) (Na(i-Pr2dtc)) against diclofenac-induced toxicity in the testes of male Wistar albino rats. The animals were assigned into six groups of six rats each. Group 1 (control) received corn oil, Groups 2, 3, 4, 5, 6 received DIC (100 mg/kg), DIC and (Na(i-Pr2dtc) (30 mg/kg), DIC and vitamin E (30 mg/kg), (Na(i-Pr2dtc) (30 mg/kg) and vitamin E only respectively. Our findings show that treatment with DIC significantly reduced superoxide dismutase (SOD) activity by 42% compared to normal control (NC) animals. In DIC treated group, Na(i-Pr2dtc) caused a 17% elevation of catalase (CAT) activity compared to DIC only group. Reduced glutathione level was significantly reduced in DIC only treated group when compared with DIC and VIT E treated group. Photomicrographs of testis from Na(i-Pr2dtc) treated rats showed normal seminiferous epithelium with no lesions. In conclusion, Na(i-Pr2dtc) has antioxidant properties.

The neonicotinoid insecticide imidacloprid has been linked to significant reproductive damage in mammals. Origanum majorana essential oil (OME) is a natural herbal product used in the management of many diseases due to its strong antioxidant effects. The oil was hydrodistilled from O. Majorana and analyzed using GC/MS then its possible protective mechanisms against IMI-induced reprotoxicity in male rats were investigated. 28-adult male Wistar rats were divided into 4 groups as follows: group (1) control group, group (2) OME, group (3) IMI, and group (4) IMI + OME. The treatments were applied daily via oral gavage for 60 days. Remarkable abnormalities in both territorial aggressive and sexual behaviors were observed in IMI-treated rats with a significant elevation of serum FSH and LH as well as altered testicular redox status. Along with inhibition of the testicular expression of StAR and aromatase genes and serum total testosterone in addition to abnormal sperm count, viability, motility, and morphology. Histopathological examination showed severe degeneration and necrosis in both germ cells and Leydig cells with atrophy in most of the seminiferous tubules. Co-administration of OME with IMI notably improved all the above-mentioned studied parameters, and restored rats\' spermatogenesis, sexual behavior, and favorably modulates the levels of both testosterone and gonadotropic hormones via its potent antioxidant effect. These findings support the use of OME as a fertility enhancer and suggest that it could be used to manage pesticide-induced male infertility.

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

The purpose of this work was to investigate the protective effect of five essential oils (EOs); Rosmarinus officinalis, Thymus vulgaris, Origanum compactum Benth., Eucalyptus globulus Labill. and Ocimum basilicum L.; against oxidative stress induced by hydrogen peroxide in Saccharomyces cerevisiae. The chemical composition of the EOs was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS). The in vitro antioxidant activity was evaluated and the protective effect of EOs was investigated. Yeast cells were pretreated with different concentrations of EOs (6.25-25 µg/ml) for an hour then incubated with H2O2 (2 mM) for an additional hour. Cell viability, antioxidants (Catalase, Superoxide dismutase and Glutathione reductase) and metabolic (Succinate dehydrogenase) enzymes, as well as the level of lipid peroxidation (LPO) and protein carbonyl content (PCO) were evaluated. The chemical composition of EOs has shown the difference qualitatively and quantitatively. Indeed, O. compactum mainly contained Carvacrol, O. basilicum was mainly composed of Linalool, T. vulgaris was rich in thymol, R. officinalis had high α-Pinene amount and for E. globulus, eucalyptol was the major compound. The EOs of basil, oregano and thyme were found to possess the highest amount of total phenolic compounds. Moreover, they have shown the best protective effect on yeast cells against oxidative stress induced by H2O2. In addition, in a dose dependent manner of EOs in yeast medium, treated cells had lower levels of LPO, lower antioxidant and metabolic enzymes activity than cells exposed to H2O2 only. The cell viability was also improved. It seems that the studied EOs are efficient natural antioxidants, which can be exploited to protect against damages and serious diseases related to oxidative stress.

Diabetes mellitus (DM) is one of the most serious threats in the 21th century throughout the human population that needs to be addressed cautiously. Nowadays, stem cell injection is considered among the most promising protocols for DM therapy; owing to its marked tissues and organs repair capability. Therefore, our 4 weeks study was undertaken to elucidate the probable beneficial effects of two types of adult mesenchymal stem cells (MSCs) on metabolism disturbance and some tissue function defects in diabetic rats. Animals were classified into 4 groups; the control group, the diabetic group, the diabetic group received a single dose of adipose tissue-derived MSCs and the diabetic group received a single dose of bone marrow-derived MSCs. Herein, both MSCs treated groups markedly reduced hyperglycemia resulting from diabetes induction via lowering serum glucose and rising insulin and C-peptide levels, compared to the diabetic group. Moreover, the increased lipid fractions levels were reverted back to near normal values as a consequence to MSCs injection compared to the diabetic untreated rats. Furthermore, both MSCs types were found to have hepato-renal protective effects indicated through the decreased serum levels of both liver and kidney functions markers in the treated diabetic rats. Taken together, our results highlighted the therapeutic benefits of both MSCs types in alleviating metabolic anomalies and hepato-renal diabetic complications.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, which is safe at therapeutic doses but can cause severe liver injury and even liver failure after overdoses. The mouse model of APAP hepatotoxicity recapitulates closely the human pathophysiology. As a result, this clinically relevant model is frequently used to study mechanisms of drug-induced liver injury and even more so to test potential therapeutic interventions. However, the complexity of the model requires a thorough understanding of the pathophysiology to obtain valid results and mechanistic information that is translatable to the clinic. However, many studies using this model are flawed, which jeopardizes the scientific and clinical relevance. The purpose of this review is to provide a framework of the model where mechanistically sound and clinically relevant data can be obtained. The discussion provides insight into the injury mechanisms and how to study it including the critical roles of drug metabolism, mitochondrial dysfunction, necrotic cell death, autophagy and the sterile inflammatory response. In addition, the most frequently made mistakes when using this model are discussed. Thus, considering these recommendations when studying APAP hepatotoxicity will facilitate the discovery of more clinically relevant interventions.

Diabetes mellitus is a well-known danger element for the progression of male reproductive dysfunctions. Available evidence supports oxidative stress to be the underlying mechanism for the manifestation of testicular dysfunctions during diabetes, and this relation represents an attractive target to antagonize these complications. Artemisia judaica L. is known to have antidiabetic and antioxidant characteristics. The possible protective effect of Artemisia judaica against diabetes-induced testicular disorders was not explored. In this investigation, we planned to estimate the possible protective effect of Artemisia judaica extract against diabetes-induced testicular disorders in male rats. The blood levels of insulin, glucose, glycosylated hemoglobin, testosterone, luteinizing hormone and follicle stimulating hormone were evaluated in rats after 12 weeks of Artemisia judaica treatment. Further, oxidative stress markers were determined in their testicular tissue. Epididymal fluid and testicular histological changes were also assessed. Expression of proliferating cell nuclear antigen has been evaluated in testis. Testicular mRNA expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 as the significant transcription factors in controlling antioxidant system were evaluated by real-time polymerase chain reaction. Artemisia judaica extracts have the ability to ameliorate the elevation in the serum glucose and blood glycosylated hemoglobin and the reduction in insulin, testosterone, follicle stimulating hormone and luteinizing hormone caused by streptozotocin-induced diabetes. It induced a significant recovery of the testicular oxidative stress markers, sperm characteristics and improved histopathological findings of the testes. Treatment with Artemisia judaica extracts led to an increase in proliferating cell nuclear antigen protein expression. Reduction of testicular oxidative stress potential in streptozotocin-treated groups was confirmed by upregulation of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1.

Phenylhydrazine (PHZ), an intermediate in the synthesis of fine chemicals is toxic for human health and environment. Despite of having severe detrimental effects on different physiological systems, exposure of erythrocytes to PHZ cause destruction of haemoglobin and membrane proteins leading to iron release and complete haemolysis of red blood cells (RBC). Involvement of oxidative stress behind such action triggers the urge for searching a potent antioxidant. The benefits of consuming olive oil is attributed to its 75% oleic acid (OA) content in average. Olive oil is the basic component of Mediterranean diet. Hence, OA has been chosen in our present in vitro study to explore its efficacy against PHZ (1 mM) induced alterations in erythrocytes. Four different concentrations of OA (0.01 nM, 0.02 nM, 0.04 nM and 0.06 nM) were primarily experimented with, among which 0.06 nM OA has shown to give maximal protection. This study demonstrates the capability of OA in preserving the morphology, intracellular antioxidant status and the activities of metabolic enzymes of RBCs that have been diminished by PHZ, through its antioxidant mechanisms. The results of the present study firmly establish OA as a promising antioxidant for conserving the health of erythrocyte from PHZ toxicity which indicate toward future possible use of OA either singly or in combination with other dietary components for protection of erythrocytes against PHZ induced toxic cellular changes.

Acetaminophen (APAP) is used as a primary drug due to its antipyretic and analgesic activity. The mechanism of action of APAP toxicity in the liver is due to the depletion of glutathione which elicited free radicals generation. Therefore, the objective of our work is to investigate the APAP induced liver damage and its repair by free radical scavenging activity of cinnamon oil (CO) in male Wistar rats. To investigate the effects of CO at different doses (50, 100 and 200 mg/kg b.w.), animals were given a single oral dose of CO per day for 14 days between 12:00-1:00 PM. The biochemical changes, imbalance in oxidative markers, interleukins, caspases and histopathological studies were determined for quantifying the hepatoprotective effect of CO. One dose of APAP (2 g/kg b.w.) results in significant hepatotoxicity and marked increase the serum markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, albumin, total protein, content of lipid peroxidation (LPO), interleukins (IL-1β, IL-6), caspase-3, -9 expression, DNA fragmentation and histopathological changes were observed. Significant decrease in the levels of LPO, interleukins IL-1β, IL-6, caspase-3, -9 expressions, qualitative as well as quantitative determination of DNA fragments and histopathological changes were reversed by the administration of CO dose dependently. Furthermore, it also restores the depleted activity of antioxidative enzymes. Our study shows that an imbalance in the oxidative parameter in the liver by APAP is restored by treating the animals with CO.

Prunus cerasus (P. cerasus) is an alternative-medicine used traditionally for amelioration of chronic-ailments marked by elevation in oxidative-stress like neuropathy. The oxidative-stress control was reported to ameliorate the inflammatory-process. This study aimed to phytochemically-investigate P. cerasus most-active phytochemicals utilizing in-vivo biological models to explore their gastroprotective, anti-inflammatory, and antinociceptive potentials and their possible mechanisms of action. Sonication with EtAc was used to extract P. cerasus fruit (Scf), and seed (Scs). The phytochemical-investigation of Scf was performed by RP-HPLC, while that of Scs was explored utilizing GC-FID. A bio-guided-fraction and isolation method was done utilizing column-chromatography, and have shown that cyanidin-3-glucoside (Cy3G) was the most-active constituent in Scf, while linoleic-acid (LA) was the most-active constituent in Scs. Scf, Scs, Cy3G, and LA significantly (p ˂ 0.05) protected the gastric-mucosa against HCl/EtOH-induced gastric-lesions. Scs (200 mg/kg) has shown the most gastroprotective-potentials, and had comparable-results to ranitidine (50 mg/kg). Scf, Scs, Cy3G, and LA have shown significant anti-inflammatory and antinociceptive potentials against carrageenan induced-edema and nociceptive-pain, respectively, where Scs (200 mg/kg) has shown the most anti-inflammatory and antinociceptive potentials, and had comparable results to ibuprofen (100 mg/kg). Scf, Scs, Cy3G, and LA have counter-acted carrageenan-induced oxidative-stress markers, with increased serum-catalase and reduced-glutathione levels, and decreased lipid-peroxidation. Histopathological-studies demonstrated gastroprotective potentials, regeneration and improvement of the spleen-structural architecture when treated with highest doses of Scs and Scf. The reduction of the pro-inflammatory TNF-alpha and IL-6, and elevation the anti-inflammatory factor IL-10 levels, spleen regenerative-capacity and oxidative-stress amelioration might be the main-mechanism responsible for P. cerasus anti-inflammatory potentials. P. cerasus appears to aid in ameliorating the inflammatory process, and reducing pain-thresholds while preserving the stomach.