Aloe vera gel relieves cadmium triggered hepatic injury via antioxidative, anti-inflammatory, and anti-apoptotic routes.

Aloe vera (AV) gel extracted from fresh AV leaves was chosen in this study to evaluate its antioxidant, anti-inflammatory, and antiapoptotic activities against cadmium (Cd) -induced liver injury. Forty Wistar male adult rats were equally divided into four groups. Group I (standard control) ingested with 2.5 ml/kg b.w. of physiological saline. Group II (Cd-intoxicated) received 3 mg/kg b.w./day of CdCl2 dissolved in saline. Group III (AV) received 200 mg/kg b.w./day of AV gel dissolved in saline. Group IV (Cd+AV) ingested with 200 mg/kg b.w./day of AV gel solution along with 3 mg/kg b.w. CdCl2. All groups were ingested orally by gavage for 3 consecutive weeks. Paraoxonase-1 (PON-1) and HSP70 were measured in serum. The deposited Cd level, nitric oxide content, lipid peroxidation, collagen-1 (COL-1), and metalloproteinase-9 (MMP-9) levels were all determined in liver tissue homogenates. Gene expression of NF-κB and IL-6, Bax, and Bcl2, as well as immunohistochemistry analysis of activated caspase-3, was performed. Results showed that ingestion of AV gel greatly relieved all oxidative stress due to Cd exposure, modulated the NF-κB, IL-6, Bax, and Bcl2 expression levels, and improved the apoptotic state. In conclusion, AV gel confirmed its potential ameliorating effect against liver injury induced due to Cd exposure.

Quercetin and L-Arginine Ameliorated the Deleterious Effects of Copper Oxide Nanoparticles on the Liver of Mice Through Anti-inflammatory and Anti-apoptotic Pathways.

The widespread use and applications of copper oxide nanoparticles (CuO NPs) in daily life make human exposure to these particles inevitable. This study was carried out to investigate the deteriorations in hepatic and serum biochemical parameters induced by CuO NPs in adult male mice and the potential ameliorative effect of L-arginine and quercetin, either alone or in combination. Seventy adult male mice were equally allocated into seven groups: untreated group, L-arginine, quercetin, CuO NPs, arginine + CuO NPs, quercetin + CuO NPs, and quercetin + arginine + CuO NPs. Treating mice with CuO NPs resulted in bioaccumulation of copper in the liver and consequent liver injury as typified by elevation of serum ALT activity, reduction in the synthetic ability of the liver indicated by a decrease in the hepatic arginase activity, and serum total protein content. This copper accumulation increased oxidative stress, lipid peroxidation, inflammation, and apoptosis as manifested by elevation in malondialdehyde, nitric oxide, tumor necrosis factor-α, the expression level of caspase-3 and bax quantified by qPCR, and the activity of caspase-3, in addition to the reduction of superoxide dismutase activity. It also resulted in severe DNA fragmentation as assessed by Comet assay and significant pathological changes in the liver architecture. The study proved the efficiency of quercetin and L-arginine in mitigating CuO NPs-induced sub-chronic liver toxicity due to their antioxidant, anti-inflammatory, and anti-apoptotic properties; ability to inhibit DNA damage; and the potential as good metal chelators. The results of histopathological analysis confirmed the biochemical and molecular studies.

Hepatoprotective effect of ferulic acid and/or low doses of γ-irradiation against cisplatin-induced liver injury in rats.

The therapeutic efficacy of cisplatin (CIS) is limited owing to its hepatotoxic side effects. The current study aimed to investigate the protective impact of ferulic acid (FA) and low-doses of γ-irradiation (LDR) against CIS-prompted hepatotoxicity in rats. Adult male Swiss albino rats were divided into eight groups: untreated group; FA, LDR, and CIS treated groups; and combinations of one or more of the above treatments. Post-treatment analyses included measuring redox markers like SOD and CAT activity, NO free radical content, and lipid peroxidation in liver tissue. Serum aminotransferase activities were also determined. Additionally, gene transcript levels of liver NF-Ò¡B-P65, caspase-1, COX-2, and IL-1ß were quantified. Moreover, immunohistochemistry for caspase-3 and histopathological examinations were estimated in liver tissue. Our findings revealed increased levels of oxidative stress along with a significant reduction in anti-oxidative responses and a significant increase in serum aminotransferase activities in the CIS-intoxicated group. A similar increase was also observed in COX-2 and IL-1ß transcript levels and caspase-3 enzyme activity, besides a decrease in transcript levels of NF-Ò¡B-p65 and caspase-1, indicating an overall inflammatory trend and an increase in the apoptotic shift. The co-administration of FA and/or treatment with LDR has ameliorated the hepatotoxic effect induced by CIS. The histopathological investigation of liver tissues confirmed this ameliorating action of these adjuvant therapies against CIS toxicity. In conclusion, it is plausible to suggest that the hepatoprotective effects of co-administration of FA and/or LDR against CIS-induced hepatotoxicity are attributed to the possession of anti-oxidative, anti-inflammatory, and anti-apoptotic capabilities.

Haptoglobin polymorphism modulates cardiometabolic impacts of four consecutive weeks, dawn to sunset Ramadan intermittent fasting among subjects with overweight/obesity.

AIMS: Haptoglobin (Hp) is a multifaceted marker of inflammation, and mediates the interplay between obesity, inflammation, and cardiometabolic dysfunction. However, the role of the Hp phenotype in modulating intermittent fasting (IF)-induced cardiometabolic changes remains to be elucidated. METHODS: Hp phenotype was determined for the study subjects. Cardiometabolic markers were assessed before and at the end of four consecutive weeks, dawn to sunset IF. RESULTS: A total of 114 subjects (75 males and 39 females, 38.7 ± 11.7 years, body mass index (BMI) of 30.41 ± 5.09 kg/m2) were recruited. Hp2-2 (n = 55, 48.2 %) and Hp2-1 (n = 53, 46.5 %) were the predominant phenotypes. Significant reductions were observed in serum Hp, IL-6, TNF-α, triglycerides (TG), total cholesterol (TC), LDL, BMI, and fat mass (FM), while a significant elevation was observed in serum CD163, HDL, and IL-10 at the end of the IF month for the whole population. Based on the Hp polymorphism, significant decreases in Hp, BMI, FM, TG, LDL, and TNF-α, with significant increases in HDL and CD163 levels were observed among subjects with Hp2-2 and Hp2-1 phenotypes. A more pronounced reduction in FM was reported in subjects with Hp2-2 in comparison with Hp2-1. CONCLUSION: Hp gene polymorphism modulates IF-induced changes in cardiometabolic markers. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN18205186; https://trialsearch.who.int/?TrialID=ISRCTN18205186.

Neuroprotective effect of sodium alginate against chromium-induced brain damage in rats.

Oral exposure to chromium hexavalent [Cr(VI)] has disastrous impacts and affects many people worldwide. Cr(VI) triggers neurotoxicity via its high oxidation potential by generating high amount of ROS. Meanwhile, alginates are known by their chelating activity and ability to bind heavy metals and toxins, in addition to their antioxidant, anti-inflammatory, and anti-apoptotic activities. So, this study aimed to explore the neuroprotective potential of sodium alginate (SA) against cellular injury, DNA damage, macromolecule alterations, and apoptosis induced by oral ingestion of Cr. Forty Wistar male rats were divided into 4 groups; group I: standard control ingested with the vehicle solution, group II: Cr-intoxicated group received 10 mg/kg b.w. of potassium dichromate orally by gavage and kept without treatment, group III: SA group in which rats were orally exposed to 200 mg/kg b.w. of SA only, and group IV: SA-treated group that received 200 mg/kg b.w. of SA along with Cr for 28 consecutive days. Neurotransmitters such as Acetyl choline esterase (AchE), Monoamine oxidase A (MAOA) concentrations, Dopamine (DA) and 5-Hydroxytryptamine (5-HT) levels were assessed in brain homogenate tissues. Neurobiochemical markers; NAD+ and S100B protein were investigated in the brain tissues and serum, respectively. Levels of HSP70, caspase-3, protein profiling were evaluated. DNA damage was determined using the Comet assay. Results revealed a significant reduction in the AchE and MAOA concentrations, DA, 5-HT, and NAD+ levels, with an increase in the S100B protein levels. Cr(VI) altered protein pattern and caused DNA damage. High levels of HSP70 and caspase-3 proteins were observed. Fortunately, oral administration of SA prevented the accumulation of Cr in brain homogenates and significantly improved all investigated parameters. SA attenuated the ROS production and relieved the oxidative stress by its active constituents. SA can protect against cellular and DNA damage and limit apoptosis. SA could be a promising neuroprotective agent against Cr(VI)-inducing toxicity.

Relevance of circulating MiRNA-21 and MiRNA-181 in prediction of glioblastoma multiforme prognosis.

BACKGROUND: Authors aimed to investigate the clinical role of miR-21 and miR-181 among glioblastoma multiforme (GBM) patients. MATERIALS AND METHODS: Expression for both miRs were detected in blood samples from newly diagnosed twenty GBM patients before and after treatment along with 20 healthy individuals using QPCR technology. RESULTS: MiR-21 reported increase expression while miR-181 reported decreased expression in GBM patients. Expression of miR-21 was up-regulated in GBM patients older than 60 years and frontal mass with tumor size > 5 cm while miR-181 expression was down-regulated among them. Worse PFS and OS reported increase in miR-21 expression and decrease in miR-181 expression. CONCLUSION: Detection of miR-21 and miR-181 expression levels may be a potential diagnostic and predictors for GBM prognosis.

Modulation of bone turnover aberration: A target for management of primary osteoporosis in experimental rat model.

Osteoporosis is a skeletal degenerative disease characterised by abnormal bone turnover with scant bone formation and overabundant bone resorption. The present approach was intended to address the potency of nanohydroxyapatite (nHA), chitosan/hydroxyapatite nanocomposites (nCh/HA) and silver/hydroxyapatite nanoparticles (nAg/HA) to modulate bone turnover deviation in primary osteoporosis induced in the experimental model. Characterisation techniques such as TEM, zeta-potential, FT-IR and XRD were used to assess the morphology, the physical as well as the chemical features of the prepared nanostructures. The in vivo experiment was conducted on forty-eight adult female rats, randomised into 6 groups (8 rats/group), (1) gonad-intact, (2) osteoporotic group, (3) osteoporotic + nHA, (4) osteoporotic + nCh/HA, (5) osteoporotic + nAg/HA and (6) osteoporotic + alendronate (ALN). After three months of treatment, serum sclerostin (SOST), bone alkaline phosphatase (BALP) and bone sialoprotein (BSP) levels were quantified using ELISA. Femur bone receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) and cathepsin K (CtsK) mRNA levels were evaluated by quantitative RT-PCR. Moreover, alizarin red S staining was applied to determine the mineralisation intensity of femur bone. Findings in the present study indicated that treatment with nHA, nCh/HA or nAg/HA leads to significant repression of serum SOST, BALP and BSP levels parallel to a significant down-regulation of RANKL and CtsK gene expression levels. On the other side, significant enhancement in the calcification intensity of femur bone has been noticed. The outcomes of this experimental setting ascertained the potentiality of nHA, nCh/HA and nAg/HA as promising nanomaterials in attenuating the excessive bone turnover in the primary osteoporotic rat model. The mechanisms behind the efficacy of the investigated nanostructures involved the obstacle of serum and tissue indices of bone resorption besides the strengthening of bone mineralisation.

Ramadan diurnal intermittent fasting modulates SOD2, TFAM, Nrf2, and sirtuins (SIRT1, SIRT3) gene expressions in subjects with overweight and obesity.

AIM: A growing body of evidence supports the impact of intermittent fasting on normalizing body metabolism and lowering oxidative stress and inflammation. Mounting evidence confirms that oxidative stress and chronic inflammation trigger the way for the development of metabolic diseases, such as diabetes. This research was conducted to evaluate the impact of Ramadan intermittent fasting (RIF) on the expression of cellular metabolism (SIRT1 and SIRT3) and antioxidant genes (TFAM, SOD2, and Nrf2). METHODS: Fifty-six (34 males and 22 females) overweight and obese subjects and six healthy body weight controls were recruited and monitored before and after Ramadan. RESULTS: Results showed that the relative gene expressions in obese subjects in comparison to counterpart expressions of controls for the antioxidant genes (TFAM, SOD2, and Nrf2) were significantly increased at the end of Ramadan, with percent increments of 90.5%, 54.1% and 411.5% for the three genes, respectively. However, the metabolism-controlling gene (SIRT3) showed a highly significant (P < 0.001) downregulation accompanied with a trend for reduction in SIRT1 gene at the end of Ramadan month, with percent decrements of 61.8% and 10.4%, respectively. Binary regression analysis revealed significant positive correlation (P < 0.05) between high energy intake (>2000 Kcal/day vs. <2000 Kcal/day) and expressions of SOD2 and TFAM (r = 0.84 and r = 0.9, respectively). CONCLUSION: Results suggest that RIF ameliorates the genetic expression of antioxidant and anti-inflammatory, and metabolic regulatory genes. Thus, RIF presumably may entail a protective impact against oxidative stress and its adverse metabolic-related derangements in non-diabetic obese patients.

Mesenchymal Stem Cells: a Promising Therapeutic Tool for Acute Kidney Injury.

Acute kidney injury (AKI) is a rapid loss of renal function. It has high mortality rates. Still, renal replacement therapy is considered the best solution for recovering AKI. This opens a line of thought to develop an alternative therapy for it without complications. Mesenchymal stem cells are considered a new therapy for treating kidney diseases. The aim of this work was to address the anti-apoptotic, antioxidative, and pro-angiogenic effects of adipose tissue-derived MSCs (AD-MSCs) and bone marrow-MSCs (BM-MSCs) for treating AKI. Adult male Wistar rats were assigned into nine groups (n = 10): (1) the control group; (2) the AKI group, receiving cisplatin; (3) the AKI group treated with AD-MSCs (1 × 106); (4) the AKI group treated with AD-MSCs (2 × 106); (5) the AKI group treated with AD-MSCs (4 × 106); (6) the AKI group treated with losartan; (7) the AKI group treated with BM-MSCs (1 × 106); (8) the AKI group treated with BM-MSCs (2 × 106); and (9) the AKI group treated with BM-MSCs (4 × 106). The results showed a significant rise in creatinine, urea, and cystatin C (cys C) levels and upregulation of p38 mRNA, whereas a significant decline in NAD(P)H quinone oxidoreductase 1 (NQO-1) protein and downregulation of B-cell lymphoma-2 (Bcl-2) mRNA and vascular endothelial growth factor (VEGF) mRNA were recorded in AKI. MSCs could improve renal functions manifested by decreased urea, creatinine, and cys C levels; downregulation of p38; and upregulation of Bcl-2 and VEGF. Moreover, MSC therapy could induce NQO-1 in the treated rats relative to the untreated rats. So, cell-based therapy can reduce AKI through the antioxidative, anti-apoptotic, and pro-angiogenic properties of MSCs. Therefore, the findings received in this attempt create a fertile base for the setup of cell therapy in patients with AKI.

Unique properties of arginase purified from camel liver cytosol.

Arginase (ARG) is an enzyme involved in urea cycle, where it catalyzes the hydrolysis of L-arginine into L-ornithine and urea. Since there is no information about the isolation and purification of ARG from camel liver, this investigation was designed to purify and characterize ARG from camel liver and compare its molecular and kinetic properties with that reported from other species. Camel liver arginase (CL-ARG) was purified to homogeneity using heat denaturation followed by ammonium sulphate precipitation with a combination of DEAE-cellulose, SP-Sepharose and Sephadex G 100-120 chromatography columns. The specific activity of CL-ARG was increased to 18,485 units/mg proteins with 23.5-fold purification over crude homogenate. It was observed that CL-ARG showed a similarity with other species such as behaviour on DEAE-cellulose column, kinetics of inhibition, necessity for metal ions as cofactor, and alkaline optimum pH. On the contrary, CL-ARG differed in its molecular weight (180kDa), oligomeric protein structure, slightly neutral-alkaline pI value (7.7), Km value (7.1mM), optimum pH (9, 10.7), and higher optimum temperature (70°C). In conclusion, this study investigated the properties of CL-ARG via a simple and reproducible purification procedure and provided valuable information for its production from available source in Egypt for medical and industrial purposes.