Acetaminophen-Induced Nephrotoxicity: Suppression of Apoptosis and Endoplasmic Reticulum Stress Using Boric Acid.

Acetaminophen (APAP) is one of the popular and safe pain medications worldwide. However, due its wide availability, it is frequently implicated in intentional or unintentional overdoses where it can cause severe liver injury and even acute liver failure. Boron is a bioactive trace element, found naturally as boric acid (BA) and borate. In this study, the effects of boric acid on the acute renal toxicity induced by APAP in rats were researched in comparison with N-acetyl cysteine (NAC). In the study, 7 groups were formed and 2 g/kg dose of paracetamol per rat was prepared by suspending in 1% Carboxy Methyl Cellulose (CMC) solution of phosphate buffer saline (PBS). Boric acid dissolved in saline was administered to experimental animals by gavage at doses of 50, 100, and 200 mg/kg. In this study, ER stress and apoptosis formed by paracetamol-induced nephrotoxicity were investigated. This purpose determined iNOS, PERK, ATF6, NFkB p53, caspases 3, 12, bcl-2, and bcl-xL gene mRNA expression kidney tissue. Also, the levels of kidney injury molecule-1 (KIM-1), Cysteine (Cys), and IL-18 levels, which are mentioned today as kidney damage markers were compared with BUN and creatine levels. The effect of boron on kidney damage was determined by histopathologic. Data were statistically analyzed by using SPSS-20 ANOVA and stated as means and standard deviation. According to the data obtained in our study, we believe that boric acid has a protective effect on the negative effects of paracetamol on the kidney. We believe that our study will provide useful data to the literature on the possibility of a supplement to be used as an active compound in paracetamol for the prophylaxis of boric acid and it can also be converted into a useful product.

The effects of boron-supplemented diets on adipogenesis-related gene expressions, anti-inflammatory, and antioxidative response in high-fat fed rats.

The fatty liver syndrome caused by nutritional factors is a common cause of hepatic dysfunction globally. This research was designed to study the shielding effect of boron in rats fed a diet having high fat. Overall, 40 Wistar albino male rats were placed into one control and four treatment groups, that is, each having eight rats. Group I was provided with a standard rat diet while group II was only provided a high-fat diet for 60 days. Groups III, IV, and V were provided with 5, 10, and 20 mg/kg/day boron, respectively, by gastric gavage besides a high-fat diet for 60 days. Malondialdehyde was increased significantly in rats' blood and tissue because of high-fat diets. Glutathione was decreased significantly in blood and tissues because of a high-fat diet. Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were decreased in the blood and tissues of the high-fat-fed rats. The genes expression for C-reactive protein, interleukin-1ß, leptin, and tumor necrosis factor-α were increased while gene expression for peroxisome proliferator-activated receptors was decreased in the liver of rats fed with a high-fat diet. Contrariwise, boron supplementation improves antioxidative response in terms of increased SOD and CAT activities, gene expression regulation, and improved anti-inflammatory activities. In a nutshell, boron has dose-dependent shielding antioxidative and tissue regenerative effects in rats.

Natural Products/Bioactive Compounds as a Source of Anticancer Drugs.

Cancer is one of the major deadly diseases globally. The alarming rise in the mortality rate due to this disease attracks attention towards discovering potent anticancer agents to overcome its mortality rate. The discovery of novel and effective anticancer agents from natural sources has been the main point of interest in pharmaceutical research because of attractive natural therapeutic agents with an immense chemical diversity in species of animals, plants, and microorganisms. More than 60% of contemporary anticancer drugs, in one form or another, have originated from natural sources. Plants and microbial species are chosen based on their composition, ecology, phytochemical, and ethnopharmacological properties. Plants and their derivatives have played a significant role in producing effective anticancer agents. Some plant derivatives include vincristine, vinblastine, irinotecan, topotecan, etoposide, podophyllotoxin, and paclitaxel. Based on their particular activity, a number of other plant-derived bioactive compounds are in the clinical development phase against cancer, such as gimatecan, elomotecan, etc. Additionally, the conjugation of natural compounds with anti-cancerous drugs, or some polymeric carriers particularly targeted to epitopes on the site of interest to tumors, can generate effective targeted treatment therapies. Cognizance from such pharmaceutical research studies would yield alternative drug development strategies through natural sources which could be economical, more reliable, and safe to use.

In vivo assessment of polydatin, a natural polyphenol compound, on arsenic-induced free radical overproduction, gene expression, and genotoxicity.

Arsenic (As) is a well-known contaminant of global groundwater. Its exposure causes several hazardous effects on animals and human via oxidative stress. The present study examined the effect of polydatin (PD) on free radical overproduction in rats exposed to As. Thirty-five male rats randomly allocated into five equal groups. To the control group, physiological saline was given orally and to the second group only 100 mg/L As was given by drinking water for 60 days. The other groups were treated with As (100 mg/L) and PD orally at 50, 100, and 200 mg/kg/day, respectively. Treatment with As enhanced malondialdehyde level but decreased glutathione level in blood, liver, kidney, brain, lung, and heart of rats. Also, As decreased superoxide dismutase and catalase activities of erythrocyte, liver, kidney, brain, lung, and heart in rats. Furthermore, As treatment gave rise to increased DNA damage and gene expressions of interleukin 1 beta (IL-1ß), nuclear factor kappa beta (NFκB), p53, and tumor necrosis factor-α (TNF-α) in the lung, brain, kidney, and liver. However, treatment of PD ameliorated As-exposed lipid peroxidation, antioxidant enzymes activities, DNA damage, gene expressions, and histopathological changes in tissues. In conclusion, PD has a dose-dependent protective effect on lipid peroxidation and antioxidant defense mechanism in rats against As exposure.

The effects of dietary boron compounds in supplemented diet on hormonal activity and some biochemical parameters in rats.

The aims of this study were to clarify the effects of dietary boric acid or borax, as a boron (B) source, on hormonal status (leptin, insulin, triiodothyronine (T3), and thyroxine) and some biochemical parameter levels as glucose, carnitine, nonesterified fatty acids, and betahydroxybutyric acid in rats. A total of 30 Sprague-Dawley male rats were divided into three equal groups: the animals in the first group (control) were fed with a standard rodent diet containing 6.4 mg B/kg, and the animals in the experimental group were fed with a standard rodent diet added with boric acid and borax (100 mg B/kg) throughout the experimental period of 28 days. The B compounds especially borax decreased leptin, insulin, and glucose levels, whereas increased T3 and carnitine levels in plasma. In addition, body weight of rats was found to be low in the boric acid group at the end of 4 weeks. Consequently, our results demonstrate that B supplementation (100 mg/kg) in diet decreases body weight, leptin, and insulin, whereas increases T3 levels in plasma, so enhances the metabolic activity of rats. Between the B compounds used in this study, it was found that borax had a greater effect on hormonal status than boric acid.

Dietary Yucca schidigera supplementation reduces arsenic-induced oxidative stress in Swiss albino mice.

The aim of this study was to clarify the effects of dietary supplementation with Yucca schidigera (Ys) on lipid peroxidation (LPO), antioxidant activity, some biochemical parameters and histopathological changes in arsenic-exposed mice. Forty Swiss albino male mice were divided into five equal groups. Group I (control group) was given normal diet and tap water for 28 days. Group II (arsenic group) was given normal diet and 100 mg/L arsenic along with drinking water for 28 days. Groups III-V were given three different doses of Ys (50, 100 and 200 mg/kg) in supplemented diet and arsenic (100 mg/L) along with drinking water throughout the entire period of 28 days. The arsenic significantly increased serum biochemical parameters and malondialdehyde levels in blood and tissue. However, arsenic significantly decreased tissue glutathione concentration, erythrocyte superoxide dismutase and catalase activities. In contrast, dietary supplementation of Ys, in a dose-dependent manner, resulted in reversal of arsenic-induced oxidative stress, LPO and activities of antioxidant enzymes. Moreover, Ys also exhibited protective action against the arsenic-induced focal gliosis and hyperemi in brain, necrosis and degeneration in liver, degeneration and dilatation in Bowman's capsule of kidney and hyaline degeneration in heart tissue of mice. Consequently, our results demonstrate that Ys especially high-dose supplementation in diet decreases arsenic-induced oxidative stress and enhances the antioxidant defence mechanism and regenerate of tissues in Swiss albino mice.

The effects of Feijoa sellowiana fruits on the antioxidant defense system, lipid peroxidation, and tissue morphology in rats.

CONTEXT: The fruits of Feijoa sellowiana Berg. (Myrtaceae) have been used to treat goiter in traditional Turkish medicine. OBJECTIVE: To evaluate the in vivo antioxidant activities of different polarities of the fruit extracts in blood and tissue (liver, kidney, brain, and heart) antioxidant defense systems in standard pellet diet and in high fat diet consumed, male rats were assessed. MATERIALS AND METHODS: The extracts (methanol, n-hexane, chloroform, ethyl acetate, n-butanol, and aqueous) were administered orally to male rats at 50 mg/kg doses daily for 4 weeks. The blood and tissue malondialdehyde (MDA), reduced glutathione (GSH) levels, plasma nitrate (NO(x)) level, total triiodothyronine (T3), thyroxine, cholesterol, triglyceride, protein, and glucose levels were determined, and erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities; plasma antioxidant activity (AOA) were experimentally studied. RESULTS: Blood MDA level (7.81 ± 0.4) was significantly decreased; GSH level (29.65 ± 1.21) and AOA (1.52 ± 0.08) were increased in ethyl acetate extract as compared with control and the other extracts. In addition, all the extracts decreased MDA levels and increased GSH levels (except brain tissue homogenate) in the tissue homogenates. Erythrocyte SOD and CAT activity levels were unchanged in F. sellowiana extracts. However, the extracts had no effect on plasma NO(x). In the histopathological examinations, any changes or damage in the vital organs were seen in animals. CONCLUSION: The experimental data demonstrated that F. sellowiana extracts displayed remarkable antioxidant activity and decreased lipid peroxidation in rats; furthermore, no histopathological changes or damage have been observed in the vital organs of rats.

The effects of dietary boric acid and borax supplementation on lipid peroxidation, antioxidant activity, and DNA damage in rats.

The aims of this study were to clarify the effects of high dietary supplementation with boric acid and borax, called boron (B) compounds, on lipid peroxidation (LPO), antioxidant activity, some vitamin levels, and DNA damage in rats. Thirty Sprague Dawley male rats were divided into three equal groups: the animals in the first group (control) were fed with a standard rodent diet containing 6.4 mg B/kg, and the animals in the experimental group were fed with a standard rodent diet added with a supra-nutritional amount of boric acid and borax (100 mg B/kg) throughout the experimental period of 28 days. The B compounds decreased malondialdehyde (MDA), DNA damage, the protein carbonyl content (PCO) level in blood, and glutathione (GSH) concentration in the liver, Cu-Zn superoxide dismutase (SOD), and catalase (CAT) activity in the kidney. The B compounds increased GSH concentration in blood and the vitamin C level in plasma. Consequently, our results demonstrate that B supplementation (100 mg/kg) in diet decreases LPO, and enhances the antioxidant defense mechanism and vitamin status. There are no differences in oxidant/antioxidant balance and biochemical parameters except for serum vitamin A and liver GSH concentration, between the boron compounds used in this study.

Beneficial effects of Aesculus hippocastanum L. seed extract on the body's own antioxidant defense system on subacute administration.

AIM OF THE STUDY: Seeds of Aesculus hippocastanum L. have long been used in European phytotherapy to treat inflammatory and vascular problems. In Turkish folk medicine, tea prepared from the crushed seeds was used to pass kidney stone and against stomach ache, while a fraction of seed was swallowed to alleviate hemorrhoids symptoms. In order to evaluate the in vivo effects of escin mixture from Aesculus hippocastanum seed on the blood and tissue antioxidant defense systems in standard pellet diet (SPD) and in high-fat diet (HFD) consumed male mice. MATERIALS AND METHODS: Escin mixture was obtained from the ethanol extract of seeds. Escin mixture was administered orally to male mice fed either standard pellet diet (SPD) or high-fat diet (HFD) at 100mg/kg doses daily for 5 weeks and the tissue (liver, kidney and heart) and blood samples were collected at the end of experimental period. The effect of escin mixture on the plasma antioxidant activity; blood and tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels; erythrocyte and tissue superoxide dismutase (SOD) and catalase activity (CAT) in SPD and HFD consumed animals were experimentally studied. RESULTS: Escin mixture prohibited the adverse effects of oxidative stress and showed a protective effect on the liver architecture both in SPD and HFD consumed male mice. Escin mixture prohibited the adverse effects of oxidative stress and showed a protective effect on the liver architecture both in SPD and HFD consumed male mice. Combined administration of high-fat diet with escin mixture decreased blood (p<0.01), liver (p<0.01), kidney (p<0.05), and heart (p<0.05) of MDA, liver SOD (p<0.01) and CAT (p<0.05) levels and increased blood (p<0.01) and liver GSH (p<0.001) levels in mice. CONCLUSION: The present results indicate that Aesculus hippocastanum increase the antioxidative defense system of the body and prevent HFD-induced lipid peroxidation in male mice.

Cholesterol-reducer, antioxidant and liver protective effects of Thymbra spicata L. var. spicata.

ETHNOPHARMACOLOGICAL RELEVANCE: Thymbra spicata is a member of the Lamiaceae family; leaves of this plant have recently gained much popularity as a remedy to combat hypercholesterolaemia. AIM OF THE STUDY: To evaluate the antihypercholesterolaemic, antioxidant and anti-steatohepatitic activities of the diethyl ether (DEE), ethyl acetate (EtOAc) and remaining aqueous (RA) extracts from Thymbra spicata var. spicata in mice. MATERIALS AND METHODS: In this study, diethyl ether, ethyl acetate and remaining aqueous extracts of Thymbra spicata L. var. spicata P.H.Davis (Lamiaceae) were evaluated for the effects on the plasma total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG) and glucose; blood malondialdehyde (MDA) and reduced glutathione (GSH); erythrocyte superoxide dismutase (SOD) and catalase activity (CAT) in mice fed with high-fat diet (HFD). RESULTS: The HFD induced an increase in plasma TC, TG, LDL, MDA concentrations compared to control group. However, administration of DEE with HFD reduced TC, LDL, TG and MDA concentrations, while increased HDL concentration, as well as GSH, SOD and CAT activities compared to HFD. The other extract from the plant was RA, which also showed a similar activity profile with DEE except CAT. On the other hand, administration of EtOAc extract with HFD decreased plasma TC, TG and MDA, while GSH concentration was increased. Histopathologically, best liver conditions were observed in DEE and lesser in RA extracts. Based on the results obtained in this investigation it is suggested that the DEE and partially RA extracts of Thymbra spicata var. spicata displayed significant antihypercholesterolaemic, antioxidant and anti-steatohepatitic activities. HPLC analysis of the DEE extract of Thymbra spicata var. spicata revealed the presence of carvacrol (44.13%). CONCLUSION: The observed cholesterol-reducer, antioxidant and liver protective effects of the DEE and partially of RA extracts of Thymbra spicata which contain mainly carvacrol indicates that these extracts possess some potential medicinal value and explain their ethnomedical use.