Circulating microRNAs as novel biomarkers for measuring the potency of ginger extract against cyclophosphamide toxicity in rat renal tissues: molecular and histopathological study.

OBJECTIVE: This study aims to explore underlying molecular variations in the expression of miRNAs in kidney tissues of ginger-treated and non-treated cyclophosphamide (CP)-intoxicated rats. MATERIALS AND METHODS:   A total of 40 adult male Wistar rats were randomly divided into four groups of 10 each: Group I (control: received normal food and water), Group II (received ginger at a dose of 300 mg/kg), Group III (received CP 75 mg/kg, i.p.), and Group IV (received the same dose of CP and ginger extract).  Rats received a single injection of 75 mg/kg CP on days 3, 4, 5, 19, 20, and 21. In CP-intoxicated rats, the treatment with ginger extract at a dose of 300 mg/kg was received by oral gavage starting seven days before CP and continuing throughout the duration of the experiment for four weeks. Molecular variations in the expression of miRNAs, apoptotic genes, histological kidney damage, and abnormal kidney function in control, ginger, and CP-intoxicated rats were identified by using real-time RT-PCR Analysis, immunohistochemical, and colorimetric assays. In addition, HPLC analysis and liquid chromatography spectrophotometry analysis using Diphenyl-1-picrylhydrazyl (DPPH) radical, and Β-Carotene-linoleic acid reagents were applied respectively for in-vitro screening of phytoconstituents and antioxidant activity for ginger extract. RESULTS: The kidney tissues of CP-intoxicated rats displayed an increase in lipid peroxidation marker malonaldehyde (MDA), DNA damage, and fibrosis markers like hyaluronic acid (HA) and hydroxyproline Hypx) with a decrease in the superoxide dismutase (SOD) and total antioxidant capacity (TAC). In addition, molecular expressions of mRNA fibrotic genes such as collagen, type 1, alpha 1 (COL1A1), and α-smooth muscle actin (αSMA). Molecular expressions of levels of B-cell lymphoma 2 (BCl-2) mRNA gene were down-regulated, and the expression of mRNA apoptotic; BCL2 associated X gene (Bax), caspase-3, Bax/BCl-2 ratio genes were significantly up-regulated respectively. Moreover, cellular oxidative genes, erythroid 2-related factor (Nrf2), and heme oxygenase-1 (HO-1) were down-regulated, respectively. The miR-155-5p, miR-34a-5p, miR-21-5p significantly increased while the miR-193b-3p, miR-455-3p, and miR-342-3p significantly decreased. Ginger also increased the expression of Nrf2, HO-1, and BCl-2 genes in the kidneys of rats induced with CP. In addition, active phytoconstituents, particularly 6]]-shogaol and 6]]-gingerol, were significantly identified in ginger extract using HPLC analysis. Antioxidant activity of these active metabolites were shown to be higher against in vitro free radicals (DPPH and Β-Carotene-linoleic acid), suggesting the potential antioxidant and antiapoptotic properties of ginger against CP-toxicity. CONCLUSIONS: Treatment with ginger in rats induced with CP resulted in significant improvement in the expression of certain molecular miRNAs. The kidney tissues of these rats showed a marked decrease in the expression of miR-155-5p, miR-34a-5p, and miR-21-5p, while the levels of miR-193b-3p, miR-455-3p, and miR-342-3p were observed to increase significantly. In conclusion, ginger can protect rats from CP-induced nephrotoxicity.

Gingerol fractions bioactivity against butanone cytotoxicity induced in newborns of mice.

OBJECTIVE: Accumulating studies have demonstrated the potential activity of ginger in treating and managing several diseases but little is known about its protective effects against teratogenicity of chemical toxins. Thus, in this study, we have evaluated the protective effect of gingerol fraction (GF) against methyl ethyl ketone (MEK) induced teratogenic effects in newborns of mice. MATERIALS AND METHODS: A total of 30 mature females and fifteen male mice (Mus musculus) weighing 25-30 g were included in this study. The pregnant mice were divided into three groups (10 mice each); control group (GI, mice received normal drinking water; NDW), methyl ethyl ketone (MEK) treated group (GII, received MEK at a dose of 350 mg/kg body weight in NDW), and GF treated group (GIII; mice received GF at a dose of 25 mg/kg in NDR). Histological analysis, cellular oxidative, and antioxidant enzymes, fibrosis, and apoptosis of brain, liver, and kidney tissues were estimated by histological and immunoassay techniques. RESULTS: In this study, the treatment of pregnant female mice with gingerol fractions (GF) at a dose of 25 mg/kg significantly protected all tissues organs of mothers and their offspring against the teratogenic effects induced by MEK at a dose of 350 mg/kg. A significant improvement in cellular antioxidant enzymes GSH, SOD, and peroxidase activities along with a reduction in the initiation of cellular oxidative free radicals (TBARS) was reported in GF treated mice compared to mice intoxicated with MEK (350 mg/kg). In addition, a significant reduction in cellular fibrosis and apoptosis was reported in all tissues of mothers and their offspring's following treatment with GF. HPLC analysis of ginger extracts estimated a set of polyphenolic compounds such [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol which are responsible for the antioxidant, anti-fibrotic, and anti-apoptotic protective effects against teratogenic effects of MEK. CONCLUSIONS: Gingerol fractions (GF) at a dose of 25 mg/kg significantly protected all tissues organs of mothers and their offspring against the teratogenic effects induced by MEK at a dose of 350 mg/kg. The beneficial effects of ginger phenolic compounds; [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol against teratogenic effects of MEK proceeded through their antioxidant, anti-fibrotic, and anti-apoptotic properties.

Efficacy of Rhus coriaria (sumac) juice in reducing muscle pain during aerobic exercise.

The main target of this study was to measure the influence of sumac juice drink on muscle indices and pain during an acute, intense exercise for 30 days. Forty healthy volunteers (15-25 years) were involved in aerobic exercise program for 4 weeks. Participants ingested sumac juice or placebo drink twice daily for 30 days. All participants were subjected for the evaluation of pain and estimation of serum: creatine kinase (CK), lactic acid dehydrogenase (LDH), troponin I, hydroxyproline (hyp), total antioxidant capacity (TAC), and in vitro antioxidant activity of sumac juice using pre-validated visual analog scale, colorimetric and immunoassays. The participants of both groups, placebo and sumac, showed an increment in pain scores both during exercise and post-exercise intervals. However, the sumac juice group showed a significant smaller increase in the pain scores compared to the placebo group. Participants in the sumac juice group were more willing to use the drink in the future. They achieved a higher satisfaction of sumac juice in ameliorating and the reduction of pain. Also, the sumac group showed a significant enhancement in the level of CK, LDH, troponin I, hyp, along with significant increase in serum (TAC) compared to the placebo group. The protective activity of muscle may relate to the antioxidant activity of phenolic component(s) in sumac juice as measured by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging (87.9%) and ß-carotene-linoleic acid (68.7%) assays. These data suggest that oral administration of sumac juice may have a beneficial effect on muscle performance among athletes.

A freeze-fracture study on the effect of neopybuthrin on the intestinal epithelial cells of Tilapia nilotica.

Freeze-fracture replicas of the plasma membrane and tight junctions (Tj) of intestinal epithelial cells were studied in Tilapia nilotica fish exposed to the pyrethroid insecticide, neopybuthrin. Exposing fishes to different repeated concentrations of 1/2 LC50 of neopybuthrin caused a significant decrease in the population density of IMPs in P- and E-faces. Tight junctions were also affected by neopybuthrin treatment. They appeared fragmented and discontinued, and their strands were fewer in number as compared with controls. Since the structure and number of Tj are major determinants of epithelial permeability, it is postulated that neopybuthrin treatment may affect the intestinal permeability of T. nilotica.

Effect of diazinon on freeze-fracture images of microvilli of intestinal epithelial cells of Tilapia nilotica.

The effect of the organophosphate insecticide, diazinon on the intramembranous particles (IMPs) of the microvilli of the intestinal epithelial cells of Tilapia nilotica fish was studied using freeze-fracture technique. Exposing fish to different repeated concentrations of diazinon (1/2LC50) caused a significant decrease in population density of IMPs in P- and E-faces. IMPs of microvilli found in intestinal epithelial cells are thought to represent many kinds of proteins including enzymes. In the present work, it is suggested that diazinon induced a reduction in enzymatic content of the membrane which was accompanied by a decrease in IMPs density of the microvilli.