A comparative study on the possible protective effect of esomeprazole, spirulina, wheatgrass on indomethacin-induced gastric ulcer in male albino rats.

Gastric ulcer is a common problem affecting the gastrointestinal tract. Spirulina and wheatgrass are natural substances that have anti-inflammatory and antioxidant effects. The aim of the Work was to elucidate the possible protective role of spirulina and wheatgrass versus standard treatment esomeprazole on indomethacin-induced gastric ulcer in adult male albino rats. Eighty adult male albino rats were divided into eight groups: group I (the control group), group II that received indomethacin (100 mg/kg orally), group III that received esomeprazole (20 mg/kg orally), group IV that received spirulina (1000 mg/kg orally), group V that received wheatgrass (1000 mg/kg orally), group VI that received indomethacin (100 mg/kg) + esomeprazole (20 mg/kg), group VII that received indomethacin (100 mg/kg) + spirulina (1000 mg/kg) and group VIII that received indomethacin (100 mg/kg) + wheatgrass (1000 mg/kg). Six hours after indomethacin treatment, all rats were anesthetized and their stomachs obtained for measures of gastric acidity, pepsin activity, mucin content, gastrin, ulcer index, total antioxidant capacity (TAC), tumor necrosis factor -α (TNF-α), interleukin-8 (IL8), proapoptotic protein (Bax). Histological (using H&E stain, PAS reaction) and immunohistochemical (using anti Ki67 immunostain) techniques were performed. Western immunoblot analysis for heat shock protein 70 (HSP70) was also done. Moreover, a morphometric study was done for area% of positive immunoreactive cells for Ki67 and optical density and area% of PAS reaction. All performed measurements were followed by statistical analysis. Indomethacin induced loss of normal architecture of gastric mucosa with sloughing of surface epithelium and inflammatory cellular infiltration. It also led to a significant increase in gastric acidity, inflammatory mediators (TNF-α, IL-8), pro-apoptotic protein Bax and a significant decrease in TAC levels and HSP-70 expression. There was also a significant decrease in area% of Ki67 immunoreactivity and area% and optical density of PAS reaction as compared with the control group and other pre-treated rats. These disturbed parameters were associated with increased ulcer index. In pre-treatment groups, the structure of the mucosa was similar to control with marked improvement in the biochemical assay. In conclusion, Spirulina and wheatgrass can partly protect the gastric mucosa against indomethacin-induced damage to a degree similar to that of the classical treatment esomeprazole.

Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms.

Reboxetine (REB) and sertraline (SER) are antidepressants. The antifungal potential of these drugs against planktonic Candida has been recently reported with limited data about their effects on Candidal biofilms. Biofilms are self-derived extracellular matrixes produced by the microbial population that is attached to biotic surfaces, such as vaginal and oral mucosa, or abiotic surfaces, such as biomedical devices, resulting in persistent fungal infections. The commonly prescribed antifungals, azoles, are usually less effective when biofilms are formed, and most of the prescribed antifungals are only fungistatic. Therefore, the current study investigates the antifungal potentials of REB and SER, alone and in combination with fluconazole (FLC) and itraconazole (ITR) against Candidal biofilms. Using proper controls, Candida species (Candida albicans, C. albicans; Candida krusei, C. krusei; and Candida glabrata, C. glabrata) were used to form biofilms in 96-well microplates. Serial dilutions corresponding to concentrations ranging from 2 to 4096 µg/mL of the target drugs (REB, SER, FLC, ITR) were prepared and added to the plates. Impairment of the biofilm biomass and biofilm metabolic viability was detected using the crystal violet (CV) assay and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, respectively. In the checkerboard assay, the sessile fractional inhibitory concentration index (SFICI) was calculated to evaluate the effects of drug combinations. SER was more effective in reducing the biomass than REB for C. albicans and C. glabrata, but both were equal for C. krusei. For the reduction in metabolic activity in C. albicans and C. glabrata, SER had a slight advantage over REB. In C. krusei, REB was slightly more potent. Overall, FLC and ITR were almost equal and produced more significant reductions in metabolic activity when compared to SER and REB, except for C. glabrata, where SER was almost equal to FLC. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of C. albicans. Synergism was detected between REB + ITR against biofilm cells of C. krusei. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of C. albicans, C. krusei, and C. glabrata. The results of the present study support the potential of SER and REB as anti-Candidal biofilm agents that are beneficial as a new antifungal to combat Candidal resistance.

The Combined Effect of Licorice Extract and Bone Marrow Mesenchymal Stem Cells on Cisplatin-Induced Hepatocellular Damage in Rats.

Drug-induced liver damage is a life-threatening disorder, and one major form of it is the hepatotoxicity induced by the drug cisplatin. In folk medicine, Licorice (Glycyrrhiza glabra (is used for detoxification and is believed to be a potent antioxidant. Currently, the magically self-renewable potential of bone marrow mesenchymal stem cells (BM-MSCs) has prompted us to explore their hepatoregenerative capability. The impact of G. glabra extract (GGE) and BM-MSCs alone and, in combination, on protecting against hepatotoxicity was tested on cisplatin-induced liver injury in rats. Hepatic damage, as revealed by liver histopathology and increased levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA), was elevated in rats by received 7 mg/kg of cisplatin intraperitoneally. The combination of GGE and BM-MSCs returned the enzyme levels to near the normal range. It also improved levels of liver superoxide dismutase (SOD) and glutathione (GSH) and reduced MDA levels. Additionally, it was found that when GGE and BM-MSCs were used together, they significantly downregulated caspase9 (Casp9), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), and interleukin-1ß (IL-1ß), which are involved in severe proinflammatory and apoptotic signaling cascades in the liver. Moreover, combining GGE and BM-MSCs led to the normal result of hepatocytes in several examined liver histological sections. Therefore, our findings suggest that GGE may have protective effects against oxidative liver damage and the promising regenerative potential of BM-MSCs.

Corrigendum to "Crinum jagus (J. Thomps. Dandy): Antioxidant and protective properties as a medicinal plant on toluene-induced oxidative stress damages in liver and kidney of rats" [Toxicol. Rep. 9 (2022) 699-712].

[This corrects the article DOI: 10.1016/j.toxrep.2022.03.026.].

Trévo abrogates Lead Acetate Neurotoxicity in Male Wistar Rats viz Antiamyloidogenesis, Antiglutaminergic, and Anticholinesterase Activities.

Background: Exposure to lead has been linked to biochemical changes similar to those patients suffering from Alzheimer's disease. Trévo is a phytonutrient-rich product with antiaging and antioxidant properties. Purpose: To investigate the neuroprotective activity of trévo against lead-induced biochemical changes in male Wistar rats. Methods: The study involves 35 animals that were randomly divided into five groups of seven rats each. Group I (Control): Orally administered distilled water; Group II (Induced): Administered 15 mg/kg of lead acetate (PbA) intraperitoneally; Group III (Treatment group): Orally administered 2 mL/kg of trévo for two days before co-administration with PbA for 12 consecutive days; Group IV (Treatment group): Orally administered 5 mL/kg of trévo for two days prior to coadministration with PbA for 12 consecutive days; Group V: Orally administered 5 mL/kg of trévo for 14 consecutive days. Animals were anesthetized with diether and the brain excised and processed for the following biochemical assays: Malonedialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GT), acetylcholinesterase (AChE), beta-amyloid, glutamate, Na+/K+ ATPase, and glutamate dehydrogenase (GD). Results: PbA caused significant oxidative stress (increased MDA concentration, decreased GSH concentration, suppressed the activity of CAT, SOD), decreased GT activity, increased activity of AChE, increased the concentration of beta-amyloid, and caused glutamate excitotoxicity (increased concentration of glutamate, decreased activity of Na+/K+ ATPase, and GD) in rat brains. Treatment with trévo at the two different doses significantly prevented oxidative damage, beta-amyloid aggregation, glutamate excitotoxicity, and acetylcholine breakdown induced by lead acetate. Conclusion: Our findings added to the reported pharmacological activity of trévo and supported the antiaging potential of trévo.

Crinum jagus (J. Thomps. Dandy): Antioxidant and protective properties as a medicinal plant on toluene-induced oxidative stress damages in liver and kidney of rats.

Crinum jagus (C. jagus; J. Thomps.) Dandy (Liliaceae) is a pantropical plant known for its medicinal values and pharmacological properties. The study assessed the protective effects and changes in oxidative stress indices due to C. jagus leaf extracts on the toluene-induced liver and kidney injuries in rats. The study was conducted on 8-week-old male Wistar rats (n = 80), weighing 243.3 ± 1.42 g. Group I, 1 ml/kg distilled water for 7 days; Group II, 4.5 ml/kg toluene once, 1 ml/kg distilled water for 7 days; Group III, 4.5 ml/kg toluene once, 500 mg/kg methanolic extract for 7 days; Group IV, 4.5 ml/kg toluene once, 500 mg/kg aqueous extract for 7 days; Group V, 500 mg/kg methanolic extract for 7 days; Group VI, 500 mg/kg aqueous extract for 7 days; Group VII, 500 mg/kg of vitamin C for 7 days; Group, VIII, 4.5 ml/kg toluene once, 500 mg/kg vitamin C for 7 days, all administrations were given by oral gavage. The phytochemical contents, absolute and relative organ weights of liver and kidneys, liver and kidney function tests, antioxidant status, as well as histological tests were analyzed using standard protocols. The tannins, flavonoids, and polyphenols were in highest concentration in both extracts, content in methanol extract (57.04 ± 1.51 mgg-1, 35.43 ± 1.03 mgg-1, 28.2 ± 0.34 mgg-1 respectively) > aqueous extract (18.74 ± 1.01 mgg-1, 13.43 ± 0.47 mgg-1, 19.65 ± 0.21 mgg-1 respectively). In the negative control group (II), bodyweights significantly (P < 0.05) reduced by 22%, liver weight and kidney weight significantly (P < 0.05) increased by 42% and 83% respectively, liver-to-bodyweight and kidney-to-bodyweight ratios increased significantly (P < 0.05); serum liver function tests (LFTs) i.e., bilirubin, alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyl transferase (GGT), and serum kidney function tests (creatinine and urea) were significantly (P < 0.05) elevated; oxidant status (tissue malondialdehyde; MDA) was significantly (P < 0.05) elevated, antioxidant status i.e., tissue superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels was significantly (P < 0.05) reduced; with markedly visible renal and hepatic histopathological findings, compared to the normal control group. In C. jagus extract test groups (III and IV), the parameters were significantly (P < 0.05) alleviated and reversed to normal/near normal compared to the negative control. The LFTs, kidney function tests, and antioxidant status were significantly (P < 0.05) more improved with the methanol extract test and standard control groups compared to the aqueous extract test group; Also, the methanol extract test group showed better histological features than the aqueous extract test and standard control groups. The methanolic extract shows better antioxidant potential due to the availability of more nonenzymatic antioxidants (tannins, flavonoids, and polyphenols). The findings showed that toluene is a very aggressive xenobiotic due to the promotion of oxidative stress and peroxidation of cellular lipids, but C. jagus leaves provide significant protection through the reducing power of nonenzymatic antioxidants and their ability to induce endogenous antioxidant enzymes (SOD, CAT, and glutathione reductase or GR) causing reduced cellular lipid peroxidation and tissue damages, quickened tissue repair, and improved cell biology of liver and kidneys during toluene toxicity. The methanol leaf extract provides better protection and should be advanced for more experimental and clinical studies to confirm its efficacy in alleviating oxidative stress tissue injuries, specifically due to toluene.

Curcumin nanoparticles have potential antioxidant effect and restore tetrahydrobiopterin levels in experimental diabetes.

Diabetes is associated with an increase in the production of free radicals, reduction of tetrahydrobiopterin (BH4, THB) levels and reduced bioavailability of nitric oxide (NO) in the vascular walls. In this contribution, we probed the effective role of curcumin nanoparticles (CUR-NPs) that prepared via solvent evaporation nanoprecipitation technique as potential system to attenuate endothelial dysfunction. In this technique, Tween 60 (polysorbate) was used as stabilizing agent for the prepared CUR-NPs and protect such nanoparticles from further agglomeration. BH4 levels and other parameters were estimated in diabetic rats. To this end, we dedicated 48 male albino rats, categorized into six groups; control (healthy rats), diabetic rats, along with four treated groups via oral administration of 0.2 mL/kg body weight/day of solutions of Tween 60 (60 mg/mL), free CUR (60 mg/mL), CUR-NPs1 (30 mg/mL), and CUR-NPs2 (60 mg/mL) for 30 days. Results showed that the mean level of malondialdehyde (MDA) has been significantly increased in diabetic group associated with a reduction of total antioxidant capacity, NO, and BH4 compared to control. These parameters were restored by the delivery of CUR-NPs - both doses in rats, compared with the two control groups that treated with Tween 60 and free CUR.