Retinoic acid reduces kidney injury by regulating oxidative stress, NRF-2, and apoptosis in hyperoxic mice.

Nuclear factor-erythroid-2-related factor-2 (NRF-2) is a cellular resistance protein to oxidants. We investigated the effect of exogenous all-trans retinoic acid (ATRA) on the antioxidant system and NRF-2 in mice kidneys under hyperoxia-induced oxidative stress. Mice were divided into four groups. Daily, two groups were given either peanut-oil/dimethyl sulfoxide (PoDMSO) mixture or 50 mg/kg ATRA. Oxidative stress was induced by hyperoxia in the remaining groups. They were treated with PoDMSO or ATRA as described above, following hyperoxia (100% oxygen) for 72 h. NRF-2 and active-caspase-3 levels, lipid peroxidation (LPO), activities of antioxidant enzymes, xanthine oxidase (XO), paraoxonase1 (PON1), lactate dehydrogenase (LDH), tissue factor (TF), and prolidase were assayed in kidneys. Hyperoxia causes kidney damage induced by oxidative stress and apoptosis. Increased LPO, LDH, TF, and XO activities and decreased PON1 and prolidase activities contributed to kidney damage in hyperoxic mice. After hyperoxia, increases in the activities of antioxidant enzymes and NRF-2 level could not prevent this damage. ATRA attenuated damage via its oxidative stress-lowering effect. The decreased LDH and TF activities increased PON1 and prolidase activities, and normalized antioxidant statuses are indicators of the positive effects of ATRA. We recommend that ATRA can be used as a renoprotective agent against oxidative stress induced-kidney damage.

Dermatoprotective effect of Moringa oleifera leaf extract on sodium valproate-induced skin damage in rats.

Valproic acid is an antiepileptic drug associated with skin-related issues like excessive hair growth, hair loss, and skin rashes. In contrast, Moringa oleifera, rich in nutrients and antioxidants, is gaining popularity worldwide for its medicinal properties. The protective properties of M. oleifera extract against skin-related side effects caused by valproic acid were investigated. Female rats were divided into control groups and experimental groups such as moringa, sodium valproate, and sodium valproate + moringa groups. A 70% ethanolic extract of moringa (0.3 g/kg/day) was given to moringa groups, and a single dose of sodium valproate (0.5 g/kg/day) was given to valproate groups for 15 days. In the skin samples, antioxidant parameters (such as glutathione, glutathione-S-transferase, superoxide dismutase, catalase, and total antioxidant capacity), as well as oxidant parameters representing oxidative stress (i.e. lipid peroxidation, sialic acid, nitric oxide, reactive oxygen species, and total oxidant capacity), were examined. Additionally, boron, hydroxyproline, sodium-potassium ATPase, and tissue factor values were determined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was also carried out for protein analysis in the skin samples. The results showed that moringa could increase glutathione, total antioxidant capacity, sodium-potassium ATPase, and boron levels, while decreasing lipid peroxidation, sialic acid, nitric oxide, total oxidant capacity, reactive oxygen species, hydroxyproline, and tissue factor levels. These findings imply that moringa possesses the potential to mitigate dermatological side effects.

Beta vulgaris L. var cicla decreases liver injury induced by antiarrhytmic agent, Amiodarone.

Amiodarone (AMD) is an effective antiarrhythmic drug, but its long-term usage strongly forms liver toxicity due to its accumulation tendency. The chard is a unique plant which has a blood sugar-lowering effect and powerful antioxidant activity. The aim of the current study was to investigate the possible protective effects of chard on AMD-induced liver injury. Male Sprague-Dawley rats were divided into four groups. Control group, aqueous chard extract given group (500 mg/kg) day for one week, AMD given group (100 mg/kg) /day for one week, AMD+Chard given group (at the same doses and times). They were sacrificed on the 8th day. The blood and liver samples were taken. The serum and liver biochemical parameters were found to be changed in AMD treated group. Chard administration reversed these parameters in serum and liver. In histological experiments, necrotic areas, mononuclear cell infiltration, the endothelial rupture in central vein, sinusoidal dilatation, hyperemia, dark eosinophilic cells and picnotic nucleus were observed in liver tissues of AMD treated group. Chard treatment reduced liver tissue damage. Considering results, we can suggest that chard prevented AMD induced liver injury biochemically and histologically.

Biochemical and Histological Effects of Moringa oleifera Extract against Valproate-Induced Kidney Damage.

Valproic acid is an effective treatment for generalized seizure and related neurological defects. Despite its efficacy and acceptability, its use is associated with adverse drug effects. Moringa oleifera leaves are rich in phytochemical and nutritional components. It has excellent antioxidant and ethnobotanical benefits, thus popular among folk medicines and nutraceuticals. In the present study, 70% ethanol extract of moringa leaves was assessed for its in vivo biochemical and histological effects against valproate-induced kidney damage. Female Sprague-Dawley rats were randomly divided into four groups: Group I: control animals given physiological saline (n = 8); Group II: Moringa extract-administered group (0.3 g/kg b.w./day, n = 8); Group III: valproate-administered animals (0.5 g/kg b.w./day, n = 15); and Group IV: valproate + moringa extract (given similar doses of both valproate and moringa extract, n = 12) administered group. Treatments were administered orally for 15 days, the animals were fasted overnight, anesthetized, and then tissue samples harvested. In the valproate-administered experimental group, serum urea and uric acid were elevated. In the kidney tissue of the valproate rats, glutathione was depleted, antioxidant enzyme activities (superoxide dismutase, catalase, glutathione reductase, glutathione S-transferase, and glutathione peroxidase) disrupted, while oxidative stress biomarker, inflammatory proteins (Tumor necrosis factor-alpha and interleukin-6), histological damage scores, and the number of PCNA-positive cells were elevated. M. oleifera attenuated all these biochemical defects through its plethora of diverse antioxidant and therapeutic properties.

Evaluating boron levels in Turkish mineral waters: a comparative study of three analytical techniques.

Turkey is abundant in natural mineral water sources, thanks to its location on the Alpine-Himalayan belt. Natural mineral water is drinking water characterized by its natural mineral, trace elements, and carbon dioxide content. Because of quite insufficient data, the boron content in bottled natural mineral waters in Turkey was analyzed by three different methods and compared: inductively coupled plasma mass spectrometry technique, carminic acid, and azomethine-H methods, in this study. The boron levels in mineral waters ranged from a minimum of 0.05 mg/L to a maximum of 8.61 mg/L. It was also safe by the upper limit level estimated by the World Health Organisation. As boron plays a beneficial role in human physiology, consuming natural mineral water may offer a positive contribution to public health by supporting boron intake in our country. The other outcome of our research was that the spectrophotometric carminic acid method can yield results similar to those obtained using the inductively coupled plasma mass spectrometry technique since the boron level of Turkish mineral water was within the limits level of the carminic acid method. However, the result of the azomethine-H method was found not to be suitable. Cross-sensitivity with other elements in mineral water might have caused this.

Effects of swimming activity and feed restriction on antioxidant and digestive enzymes in juvenile rainbow trout: Implications for nutritional and exercise strategies in aquaculture.

BACKGROUND: In this study, we investigated the effects of swimming activity and feed restriction on digestion and antioxidant enzyme activities in juvenile rainbow trout (average body weight of 26.54 ± 0.36 g). METHODS: The stomach, liver and kidney tissues were obtained from four distinct groups: the static water group (fish were kept in static water and fed to satiation), the feeding restricted group (fish were kept in static water with a 25% feed restriction), the swimming exercised group (fish were forced to swimming at a flow rate of 1 Body Length per second (BL/s)) and the swimming exercised-feed restricted group (subjected to swimming exercise at a 1 BL/s flow rate along with a 25% feed restriction). We determined the levels of glutathione, lipid peroxidation and the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and lactate dehydrogenase, as well as the presence of reactive oxygen species in the tissues obtained from the fish. Additionally, the activities of pepsin, protease, lipase and arginase in these tissues were measured. RESULTS: Swimming activity and feed restriction showed different effects on the enzyme activities of the fish in the experimental groups. CONCLUSION: It can be concluded that proper nutrition and exercise positively influence the antioxidant system and enzyme activities in fish, reducing the formation of free radicals. This situation is likely to contribute to the fish's development.

Purification and characterization of glutamate dehydrogenase from rainbow trout (Oncorhynchus mykiss) liver and molecular docking studies.

Glutamate dehydrogenase (GDH) participates in the energy metabolism of proteins and the synthesis of metabolites important for the organism. In this study, GDH enzyme was purified from the liver of rainbow trout (Oncorhynchus mykiss) by 2',5'-ADP Sepharose 4B affinity chromatography in one step. As a result of this purification process, GDH enzyme was purified 171-fold with 5.83 U/mg protein-specific activity. The characterization experiments presented that the storage stability of the purified GDH enzyme was determined as -80°C; optimum temperature 40°C; it was determined that the optimum ionic strength was 100 mM phosphate buffer and the optimum pH was 8.00. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and PAGE studies showed that the natural molar mass of the purified GDH enzyme was 346.74 kDa, and the molar mass of its subunits was 53.71 kDa. Km and Vmax values for substrates and coenzymes of GDH enzyme purified from rainbow trout liver were calculated, and the lowest Km value was found in NAD+ (1.86 mM) and the highest Vmax value in NH4 + (1.79 U/mL). The effects of some metal ions, vitamins, and solvents on the activity of the purified GDH enzyme were investigated and also IC50 values and inhibition types. The metal ion with the lowest IC50 value is Ag+ (8.65 ± 1.68 µM), and the vitamin is B6 (0.77 ± 0.04 mM). The binding affinities of inhibitors were investigated with molecular docking, based on the conformational state of GDH.

The effect of different types of microplastic and acute cadmium exposure on the Mytilus galloprovincialis (Lamarck, 1819).

Microplastic (MP) pollution is a pressing issue for both environmental health and the safety of human food sources. This study provides a comprehensive analysis of the effects of MPs on Mediterranean mussels (Mytilus galloprovincialis, Lamarck 1819), focusing on the food safety risks associated with MP and cadmium (Cd) exposure in these organisms intended for consumption. The retention of different polymer types of MPs in mussels was specifically evaluated, and the influence of Cd on MP retention across these polymers was investigated. Mussels were exposed to polystyrene (PS), polypropylene (PP), and polyethylene terephthalate (PET) MPs individually and in combination with the toxic metal Cd for a duration of 7 days. Antioxidant enzymes, oxidative stress parameters, and digestive system enzyme activities, selected as biomarkers for Cd and MPs pollution, were assessed. Furthermore, human consumption risk evaluations and limits regarding mussel intake were analysed in terms of food safety. The results suggest that exposure to Cd, MPs, or their combination induces oxidative stress, tissue damage, and neurotoxicity. Alterations in digestive enzyme activities could impact the mussels' energy acquisition from food and their capacity to conserve energy reserves. The estimated daily intake (EDI), provisional tolerable weekly intake (PTWI), target hazard quotient (THQ), and target cancer risk (TCR) levels for all groups surpassed established limits, implying a significant health risk for humans consuming these products. These results underscore the potential health risks for humans associated with consuming mussels exposed to Cd and/or MPs and provide valuable data for monitoring pollution levels and ecological risks in aquatic organisms. Additionally, our findings reveal that the retention of Cd in mussel tissues varies significantly after exposure, with combinations of PET and Cd showing lower levels of Cd accumulation compared to other groups, suggesting a differential interaction that influences Cd retention.

Evaluation of biotoxins and toxic metal risks in mussels from the Sea of Marmara following marine mucilage.

The mucilage phenomenon observed in the Sea of Marmara in 2021, has raised public concern about seafood safety. Mediterranean mussels serve as a vehicle in food chain, enabling the transfer of pollutants. Farmed and wild mussels were collected from 4 different stations throughout the fishing season. Biotoxins causing amnesic, paralytic, or diarrhetic shellfish poisonings (ASP, PSP, or DSP) were examined during monthly samplings. Potential health risks posed by cadmium, lead and arsenic were assessed. Health risks were evaluated considering 150 g/week mussel consumption, accounting for the different age groups of consumers (50, 60, 70 kg). Estimated Weekly Intake calculations of metals were determined to be lower than Provisional Tolerable Weekly Intake at all age groups throughout the sampling period in all stations. Target Hazard QuotientCd of mussels captured from Istanbul Strait was always determined <1, while it was equal to 1 for 50 kg individuals in Gelibolu samples. All THQAs were >1. Target carcinogenic Risk was evaluated for Pb and iAs, which were found to be negligible and acceptable, respectively. No biotoxins responsible for ASP, PSP, or DSP were detected. Hg levels were under detectable limits. Excluding Cd, the results did not reveal any risks associated with mussel consumption during mucilage.

Reversal of Valproate-Induced Major Salivary Gland Changes By Moringa Oleifera Extract in Rats.

This study aimed to explore the potential protective impacts of Moringa oleifera extract on major alteration in salivary glands of rats exposed to sodium valproate (VA). Groups were defined as control, control+moringa extract, sodium valproate, and sodium valproate+moringa extract. Antioxidant and oxidant status, activities of digestive and metabolic enzymes were examined. VA treatment led to various biochemical changes in the salivary glands, including decreased levels of antioxidants like glutathione, glutathione-S-transferase, and superoxide dismutase (except for sublingual superoxide dismutase). Conversely, a decrease in alpha-amylase, alkaline and acid phosphatase, lactate dehydrogenase, protease, and maltase activities were observed. The study also demonstrated that VA induces oxidative stress, increases lipid peroxidation, sialic acid, and nitric oxide levels in the salivary glands. Total oxidant capacity was raised in all glands except in the sublingual gland. The electrophoretic patterns of proteins were similar. Moringa oleifera extract exhibited protective properties, reversing these VA-induced biochemical changes due to its antioxidant and therapeutic attributes. This research suggests that moringa extract might serve as an alternative treatment approach for individuals using VA and experiencing salivary gland issues, although further research is necessary to confirm these findings in human subjects.

Antioxidant Activity and Protective Effects of an Oxovanadium (IV) Complex on Heart and Aorta Injury of STZ-Diabetic Rats.

Diabetic people have a much higher rate of cardiovascular disease than healthy people. Therefore, heart and aortic tissues are target tissues in diabetic research. In recent years, the synthesis of new vanadium complexes and investigation of their antidiabetic/lowering effect on the blood glucose levels and antioxidant properties are increasing day by day. Our study aimed to examine the effects of synthesized oxovanadium (IV) complex of 2-[(2,4-dihydroxybenzylidene]hydrazine-1-[(N-(2-hydroxybenzylidene)](S-methyl)carbothioamide [VOL] on diabetic heart and aortic tissues, as well as in vitro lactate dehydrogenase (LDH) and myeloperoxidase (MPO) inhibition, antioxidant properties, and reducing power. Electrochemical characterization of the VOL was carried out by using Cyclic Voltammetry (CV) and Linear Sweep Voltammetry (LSV) methods. In addition, in silico drug-likeness and ADME prediction were also investigated. For in vivo study, male Swiss albino rats were randomly selected and separated into four groups which are control, control + VOL, diabetic and diabetic + VOL. After the experimental procedure, biochemical parameters were investigated in homogenates of heart and aorta tissues. The results showed that VOL has a protective effect on heart and aortic tissue against oxidative stress. According to electrochemical experiments, one reversible oxidative couple and one irreversible reductive response were observed for the complex. In addition, in vitro LDH and MPO inhibition of VOL was examined. It was found that VOL had a protective effect on heart and aortic tissues of diabetic rats, and caused the inhibition of LDH and MPO in in vitro studies. On the other hand, evaluating the synthesized VOL according to in silico drug-likeness and absorption, distribution, metabolism, and excretion (ADME) prediction, it was found that VOL has drug-like properties and exhibited high gastrointestinal absorption. The VOL had a therapeutic impact on the heart and aortic tissues of diabetic rats, according to the findings.

Purification and characterization of thioredoxin reductase enzyme from commercial Spirulina platensis tablets by affinity chromatography and investigation of the effects of some chemicals and drugs on enzyme activity.

Thioredoxin reductase (TrxR, enzyme code [E.C.] 1.6.4.5) is a widely distributed flavoenzyme that catalyzes nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of thioredoxin and many other physiologically important substrates. Spirulina platensis is a blue-green algae that is often used as a dietary supplement. S. platensis is rich in protein, lipid, polysaccharide, pigment, carotenoid, enzyme, vitamins and many other chemicals and exhibits a variety of pharmacological functions. In the present study, a simple and efficient method to purify TrxR from S. platensis tablets is reported. The extractions were carried out using two different methods: heat denaturation and 2',5'-adenosine diphosphate Sepharose 4B affinity chromatography. The enzyme was purified by 415.04-fold over the crude extract, with a 19% yield, and specific activity of 0.7640 U/mg protein. Optimum pH, temperature and ionic strength of the enzyme activity, as well as the Michaelis constant (Km ) and maximum velocity of enzyme (Vmax ) values for NADPH and 5,5'-dithiobis(2-nitrobenzoic acid) were determined. Tested metal ions, vitamins, and drugs showed inhibition effects, except Se4+ ion, cefazolin sodium, teicoplanin, and tobramycin that increased the enzyme activity in vitro. Ag+ , Cu2+ , Mg2+ , Ni2+ , Pb2+ , Zn2+ , Al3+ , Cr3+ , Fe3+ , and V4+ ions; vitamin B3 , vitamin B6 , vitamin C, and vitamin U and aciclovir, azithromycin, benzyladenine, ceftriaxone sodium, clarithromycin, diclofenac, gibberellic acid, glurenorm, indole-3-butyric acid, ketorolac, metformin, mupirocin, mupirocin calcium, paracetamol, and tenofovir had inhibitory effects on TrxR. Ag+ exhibited stronger inhibition than 1-chloro-2,4-dinitrobenzene (a positive control).

Purification of thioredoxin reductase from Spirulina platensis by affinity chromatography and investigation of kinetic properties.

The thioredoxin system consists of thioredoxin (Trx), thioredoxin reductase (TrxR) and nicotinamide adenine dinucleotide phosphate (NADPH). Spirulina platensis, which is one of the blue-green algae in the form of spiral rings, belongs to the cyanobacteria class. Spirulina platensis can produce Trx under stress conditions. If it can produce Trx, it also has TrxR activity. Therefore, in this study, the TrxR enzyme was purified for the first time from Spirulina platensis, an algae the most grown and also used as a nutritional supplement in the world. A two-step purification process was used: preparation of the homogenate and 2',5'-ADP sepharose 4B affinity chromatography. The enzyme was purified with a purification fold of 1059.51, a recovery yield of 9.7 %, and a specific activity of 5.77 U/mg protein. The purified TrxR was tested for purity by SDS-PAGE. The molecular weight of its subunit was found to be about 45 kDa. Optimum pH, temperature and ionic strength of the enzyme were pH 7.0, 40 °C and 750 mM in phosphate buffer respectively. The Michaelis constant (Km) and maximum velocity of enzyme (Vmax) values for NADPH and 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) are 5 µM and 2.2 mM, and 0.0033 U/mL and 0.0044 U/mL, respectively. Storage stability of the purified enzyme was determined at several temperatures. The inhibition effects of Ag+, Cu2+, Al3+ and Se4+ metal ions on the purified TrxR activity were investigated in vitro. While Se4+ ion increased the enzyme activity, other tested metal ions showed different type of inhibitory effects on the Lineweaver-Burk graphs.

The evaluations of the inhibition of orlistat on Clostridium perfringens sialidase (NanI) activity by in†vitro and in silico approaches.

Clostridium perfringens (C. perfringens) is a bacterium that causes serious problems in humans and animals such as food poisoning, gas gangrene and infections. C. perfringens has three sialidases (NanH, NanI, NanJ) and inhibition of NanI constitutes an approach in the treatment of C. perfringens since NanI provides the carbohydrate source necessary for the growth of bacteria. In our study, the inhibition effect of some drugs belonging to different drug groups on NanI activity was investigated. Among these drugs, orlistat (0.21±0.05 µM) was determined to have a lower IC50 value than the positive control quercetin (15.58±1.59 µM). It was determined in vitro by spectrofluorometric method. Additionally, NanI molecular docking studies with orlistatand quercetin were performed using iGemdock, DockThor and SwissDock. Orlistat (-93.93, -8.649 and -10.03 kcal/mol, respectively) was found to have a higher binding affinity than quercetin (-92.68, -7.491 and -8.70 kcal/mol, respectively), and the results were in line with in vitro studies. The results may suggest that orlistat is a molecule with drug potential for C. perfringens because it inhibits the drug target NanI, and that the inhibition efficiency can be increased by studies with orlistat derivatives.

Glycoprotein Levels and Oxidative Stomach Damage in Diabetes and Prostate Cancer Model: Protective Effect of Metformin.

Men with diabetes have a higher risk of prostate cancer and people with prostate cancer are prone to stomach metastases. Therefore, researchers are continuing in order to find new approaches in the treatment of individuals with both diseases at the same time. The protective effect of metformin (which is used in the treatment of diabetes) on cancer continues to be supported by studies. The present study aimed that the protective effect of metformin in the stomach tissue of diabetic and/or prostate cancer rats was investigated through biochemical parameters. In the study, it was determined that the biochemical parameters studied showed a protective effect on stomach tissues with the administration of metformin to cancer and diabetic+cancer groups, and as a result of the principal component analysis, it was determined that the biochemical parameters studied in the stomach tissue showed a correlation.

Petroselinum crispum Extract Prevents Scopolamine-Induced Lens Damage in Rats.

Alzheimer's disease (AD) is a neurodegenerative disease that occurs especially in advanced ages. It reduces the quality of life of both the patient and their relatives. In addition to its primary effects, AD causes metabolic defects and tissues are damaged due to these effects. Oxidative stress damages cells by disrupting antioxidant/oxidant balance in many tissues, especially due to AD. In individuals with AD and the elderly, lens tissue is damaged due to oxidative stress and may cause vision loss. Therefore, it is very important to investigate herbal products that both prevent/cure AD and reduce AD-related oxidative stress, as they may have fewer side effects. In this study, the protective effects of parsley (Petroselinum crispum) extract on lens tissues of an experimental AD model induced by scopolamine were examined and evaluated through biochemical parameters. The result of biochemical experiments and principal component analysis, was observed that parsley extract had a therapeutic effect by reducing oxidative stress in lens tissues of experimentally induced AD rats. It can be suggested that the phenolic and flavonoid-rich content of parsley extract may have caused the reduction of oxidative damage in lens tissues and can be used to protect lens tissue against oxidative stress due to AD disease.

Oxidative brain and cerebellum injury in diabetes and prostate cancer model: Protective effect of metformin.

The body can host the spread of prostate cancer cells. Metastases from prostate cancer are more frequently seen in the brain, liver, lungs, and lymph nodes. A well-known antidiabetic drug, metformin, is also known to have antitumor effects. Our study focuses on the evaluation of potential metformin protective effects on brain and cerebellum damage in streptozotocin (STZ)-induced diabetic and Dunning prostate cancer models. In this investigation, six groups of male Copenhagen rats were created: control, diabetic (D), cancer (C), diabetic + cancer (DC), cancer + metformin, and diabetic + cancer + metformin. The brain and cerebellum tissues of the rats were taken after sacrifice. Oxidative stress markers including reduced glutathione level, lipid peroxidation, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase activities, reactive oxygen species, total oxidant and total antioxidant status, lactate dehydrogenase, xanthine oxidase, acetylcholinesterase activities, protein carbonyl contents, nitric oxide and OH-proline levels, sodium potassium ATPase, carbonic anhydrase, and glucose-6-phosphate dehydrogenase activities; glycoprotein levels including hexose, hexosamine, fucose, and sialic acid levels; and histone deacetylase activity as a cancer marker were determined. Oxidative stress markers were impaired and glycoprotein levels and histone deacetylase activity were increased in the D, C, and DC groups. Metformin therapy reversed these effects. Metformin was found to protect the brain and cerebellum of STZ-induced diabetic rats with Dunning prostate cancer from harm caused by MAT-Lylu metastatic cells.

Drug repurposing: Metformin's effect against liver tissue damage in diabetes and prostate cancer model.

Background: There are evidences linking diabetes to the pathogenesis and progression of various cancers. Metformin is a well-known antidiabetic drug that reduces the levels of circulating glucose and insulin in patients with both insulin resistance and hyperinsulinemia. Aim of the present study was to evaluate the effect of metformin on the liver of rats bearing prostate cancer, diabetes and prostate cancer + diabetes via histopathological and biochemical methods. Methods: Male Copenhagen rats were divided into six groups. Control group, diabetic group, cancer group, diabetic + cancer group, diabetic + cancer + metformin group, cancer + metformin group. Diabetes was induced by injecting single dose of streptozotocin (65 mg/kg) to Copenhagen rats, cancer induced 2 × 104 Mat-LyLu cells. Metformin treatment was administered daily by gavage following inocculation of the Mat- Lylu cells to fifth and sixth group. The experiment was terminated on the 14th day following Mat-LyLu cell injection. At the end of the experimental period, the rats were sacrificed, and liver tissue was taken. Liver damage was scored. Biochemically, serum prostate-specific antigen level was determined by employing Enzyme Linked Immuno Sorbent Assay method. In addition, the activities of different enzyme and biochemical parameters were determined spectrophotometrically inform the hepatic tissue specimens. Results: The findings of this study reveal that histopathological and biochemical damage in cancer and diabetic + cancer groups decreased significantly in the metformin treated groups. Conclusion: These highlights that the antidiabetic drug metformin can be repositioned for attenuating liver tissue damage associated with prostate cancer and diabetes.

Melatonin improves liver and pancreatic tissue injuries in diabetic rats: role on antioxidant enzymes.

Purpose: Melatonin (Mel) is an indolamine mainly synthesized by the pineal gland and many other organs. It plays an important role in scavenging free radicals and stimulating antioxidant enzymes. The goal of this study was to investigate the effect of Mel and/or insulin treatment on oxidative liver and pancreas injuries in diabetic rats. Methods: Male Wistar albino rats were assigned into 5 groups. Group I: control animals. Group II: diabetes was induced via a single dose of STZ (60 mg/kg) administered intraperitoneally. Group III: diabetic rats treated with Mel (10 mg/kg/day). Group IV: diabetic rats given insulin (6U/kg) subcutaneously. Group V: diabetic rats that received insulin and Mel at the same dose and time. After 12 weeks of the experiment, the animals were decapitated, liver and pancreas tissues were collected. Results: The results indicated that reduced glutathione levels in liver and pancreatic tissue decreased, while protein carbonyl, advanced oxidized protein products and lipid peroxidation levels were elevated in diabetic group. Antioxidant enzyme activities decreased in liver tissues but increased in pancreatic tissues of the diabetic group. Administration of Mel, insulin or Mel + insulin reversed these biochemical changes in the diabetic animals. Conclusion: This work shows that in long-term oxidative stress conditions caused by STZ-induced diabetes, either Mel or Mel + insulin administration may improve the deteriorated oxidant/antioxidant system in both the liver and pancreas tissues. These results suggested that Mel alone or Mel + insulin treatments might have a significant role in protecting against liver and pancreatic damage in STZ diabetic rats via different antioxidant effects.

Effect of Moringa oleifera leaf extract on valproate-induced oxidative damage in muscle.

Valproic acid (VPA) is a drug used for the treatment of epilepsy worldwide. Depending on usage, it can cause complications such as coagulopathies, hepatotoxicity, and encephalopathy. Moringa oleifera has been shown to have antitumor, anti-inflammatory, antiulcer, antispasmodic, diuretic, antihypertensive, antidiabetic, and hepatoprotective activities. The current study investigated the effects of Moringa leaves extract (70% ethanol) on antioxidant systems against valproate-induced oxidative damage in muscle tissues of rats. Female Sprague Dawley rats were randomly divided into four groups. Group I: control group; Group II: animals given only Moringa extract; Group III: animals that received only sodium valproate; Group IV: animals administered with sodium valproate + Moringa extract. Moringa extract and sodium valproate were administered orally. Muscle tissues were collected after sacrificing the animals. Biochemical analysis of muscle tissue homogenates of the valproate group revealed elevated levels/activities of lipid peroxidation, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, catalase, glutathione reductase, glutathione-S-transferase, reactive oxygen species, total oxidant status, oxidative stress index, glucose-6-phosphate dehydrogenase, sialic acid, protein carbonyl, nitric oxide, and myeloperoxidase. While glutathione, superoxide dismutase, glutathione peroxidase, total antioxidant status, aryl esterase and sodium/potassium ATPase were decreased. The administration of Moringa extract reversed these biochemical changes. These results indicate that Moringa leaves extract had a protective effect on muscle tissues against valproate-induced damage.