The nephroprotective effects of allicin and ascorbic acid against cisplatin-induced toxicity in rats

International audienceCisplatin (CDDP) may induce nephrotoxicity through oxidative stress, DNA damage, and inflammation. This study was performed to evaluate the antioxidant and anti-inflammatory effects of allicin and ascorbic acid (AA) and investigate the nephroprotective efficacy of their combination against CDDP-induced intoxication. Rats were divided into seven groups: control, allicin (10 mg/kg for 14 days), AA (20 mg/kg for 14 days), CDDP (7 mg/kg as a single dose on the seventh experimental day), CDDP-allicin, CDDP-AA, and CDDP-allicin-AA (at the aforementioned doses). The administration of CDDP induced marked body weight loss and renal damage, manifested by significant increases (p < 0.05) in serum creatinine, urea, and uric acid levels and significant reductions in serum Na, Ca, and phosphorus concentrations, in addition to severe alterations in serum and renal tissue levels of tumor necrosis factor-α in comparison with control rats. Moreover, CDDP-intoxicated rats exhibited significantly (p < 0.05) higher lipid peroxidation, as well as lower levels of reduced glutathione and activities of glutathione peroxidase,superoxide dismutase, and catalase enzymes in the renal tissue, compared with control rats. The administration of allicin or AA significantly reduced (p < 0.05) the CDDP-induced changes in all the aforementioned parameters. Interestingly, allicin achieved comparable nephroprotection to AA in most assessed parameters; however, the restoration of normal serum and renal tissue concentrations of these parameters was more frequent in the CDDP-AA group. In conclusion, both allicin and AA showed significant nephroprotective effects against CDDP intoxication and their combination exhibited better protection than either agent alone. These results are probably mediated by their antioxidant and anti-inflammatory activities

Influence of Spirulina platensis and ascorbic acid on amikacin-induced nephrotoxicity in rabbits

International audienceThe current study was performed to investigate the nephroprotective efficacy of Spirulina platensis (SP) and the possible benefits of combining SP and ascorbic acid (AA) in protecting against amikacin (AMK)-induced nephrotoxicity in rabbits. Forty-two male New Zealand rabbits were allocated to seven equal groups, receiving (I) normal saline as negative controls, (II) oral SP (500 mg/kg body weight), (III) oral AA (20 mg/kg bw), (IV) intramuscular AMK injection (100 mg/kg bw), (V) AMK plus SP, (VI) AMK plus AA, or (VII) AMK plus SP and AA at the aforementioned doses. The treatments were given once/day for 7 days. Data analysis showed that in comparison to the control group, AMK-intoxicated rabbits showed significant increases (p ≤ 0.05) in serum concentrations of creatinine, uric acid, and urea, as well as renal tissue concentrations of tumor necrosis factor-α [TNF-α], malondialdehyde [MDA], and nitric oxide [NO]. Moreover, significant (p ≤ 0.05) reductions in renal glutathioneconcentration, antioxidant enzymatic activities (catalase, glutathione peroxidase, and superoxide dismutase), and total antioxidant capacity were noted following AMK intoxication. Treatment by SP ameliorated most of the aforementioned AMK-induced alterations. Although treatment with AA significantly reduced the renal tissue MDA, NO, and TNF-α concentrations, it was not associated with significant ameliorations of AMK-induced changes in the serum concentrations of renal function markers or renal tissue antioxidant parameters. The nephroprotective effects of SP-AA combination were more potent than SP alone in several parameters. In conclusion, SP alone or in combination with AA minimized the nephrotoxic effects of AMK through their antioxidant and anti-inflammatory activities

A Comprehensive In Silico Exploration of Pharmacological Properties, Bioactivities, Molecular Docking, and Anticancer Potential of Vieloplain F from Xylopia vielana Targeting B-Raf Kinase

Compounds derived from plants have several anticancer properties. In the current study, one guaiane-type sesquiterpene dimer, vieloplain F, isolated from Xylopia vielana species, was tested against B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma. A comprehensive in silico analysis was conducted in this research to understand the pharmacological properties of a compound encompassing absorption, distribution, metabolism, excretion, and toxicity (ADMET), bioactivity score predictions, and molecular docking. During ADMET estimations, the FDA-approved medicine vemurafenib was hepatotoxic, cytochrome-inhibiting, and non-cardiotoxic compared to the vieloplain F. The bioactivity scores of vieloplain F were active for nuclear receptor ligand and enzyme inhibitor. During molecular docking experiments, the compound vieloplain F has displayed a higher binding potential with &minus;11.8 kcal/mol energy than control vemurafenib &minus;10.2 kcal/mol. It was shown that intermolecular interaction with the B-Raf complex and the enzyme&rsquo;s active gorge through hydrogen bonding and hydrophobic contacts was very accurate for the compound vieloplain F, which was then examined for MD simulations. In addition, simulations using MM-GBSA showed that vieloplain F had the greatest propensity to bind to active site residues. The vieloplain F has predominantly represented a more robust profile compared to control vemurafenib, and these results opened the road for vieloplain F for its utilization as a plausible anti-melanoma agent and anticancer drug in the next era

Antagonistic effects of Spirulina platensis on diazinon-induced hemato-biochemical alterations and oxidative stress in rats

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nCOVID-19 Pandemic: From Molecular Pathogenesis to Potential Investigational Therapeutics

International audienceIn December 2019, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related epidemic was first observed in Wuhan, China. In 2020, owing to the highly infectious and deadly nature of the virus, this widespread novel coronavirus disease 2019 (nCOVID-19) became a worldwide pandemic. Studies have revealed that various environmental factors including temperature, humidity, and air pollution may also affect the transmission pattern of COVID-19. Unfortunately, still, there is no specific drug that has been validated in large-scale studies to treat patients with confirmed nCOVID-19. However, remdesivir, an inhibitor of RNA-dependent RNA polymerase (RdRp), has appeared as an auspicious antiviral drug. Currently, a large-scale study on remdesivir (i.e., 200 mg on first day, then 100 mg once/day) is ongoing to evaluate its clinical efficacy to treat nCOVID-19. Good antiviral activity against SARS-CoV-2 was not observed with the use of lopinavir/ritonavir (LPV/r). Nonetheless, the combination of umifenovir and LPV/r was found to have better antiviral activity. Furthermore, a combination of hydroxychloroquine (i.e., 200 mg 3 times/day) and azithromycin (i.e., 500 mg on first day, then 250 mg/day from day 2–5) also exhibited good activity. Currently, there are also ongoing studies to evaluate the efficacy of teicoplanin and monoclonal and polyclonal antibodies against SARS-CoV-2. Thus, in this article, wehave analyzed the genetic diversity and molecular pathogenesis of nCOVID-19. We also present possible therapeutic options for nCOVID-19 patients

Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer's Disease

Alzheimer's disease (AD) is an irreversible chronic neurodegenerative disorder that occurs when neurons in the brain degenerate and die. Pain frequently arises in older patients with neurodegenerative diseases including AD. However, the presence of pain in older people is usually overlooked with cognitive dysfunctions. Most of the times dementia patients experience moderate to severe pain but the development of severe cognitive dysfunctions tremendously affects their capability to express the presence of pain. Currently, there are no effective treatments against AD that emphasize the necessity for increasing research to develop novel drugs for treating or preventing the disease process. Furthermore, the prospective therapeutic use of cannabinoids in AD has been studied for the past few years. In this regard, targeting the endocannabinoid system has considered as a probable therapeutic strategy to control several associated pathological pathways, such as mitochondrial dysfunction, excitotoxicity, oxidative stress, and neuroinflammation for the management of AD. In this review, we focus on recent studies about the role of cannabinoids for the treatment of pain and related neuropathological changes in AD

GC-MS Analysis and Biomedical Therapy of Oil from n-Hexane Fraction of <i>Scutellaria edelbergii Rech</i>. f.: In Vitro, In Vivo, and In Silico Approach

The current study aimed to explore the crude oils obtained from the n-hexane fraction of Scutellaria edelbergii and further analyzed, for the first time, for their chemical composition, in vitro antibacterial, antifungal, antioxidant, antidiabetic, and in vivo anti-inflammatory, and analgesic activities. For the phytochemical composition, the oils proceeded to gas chromatography-mass spectrometry (GC-MS) analysis and from the resultant chromatogram, 42 bioactive constituents were identified. Among them, the major components were linoleic acid ethyl ester (19.67%) followed by ethyl oleate (18.45%), linolenic acid methyl ester (11.67%), and palmitic acid ethyl ester (11.01%). Tetrazolium 96-well plate MTT assay and agar-well diffusion methods were used to evaluate the isolated oil for its minimum inhibitory concentrations (MIC), minimum bactericidal concentration (MBC), half-maximal inhibitory concentrations (IC50), and zone of inhibitions that could determine the potential antimicrobial efficacy’s. Substantial antibacterial activities were observed against the clinical isolates comprising of three Gram-negative bacteria, viz., Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and one Gram-positive bacterial strain, Enterococcus faecalis. The oils were also effective against Candida albicans and Fusarium oxysporum when evaluated for their antifungal potential. Moreover, significant antioxidant potential with IC50 values of 136.4 and 161.5 µg/mL for extracted oil was evaluated through DPPH (1,1-Diphenyl-2-picryl-hydrazyl) and ABTS assays compared with standard ascorbic acid where the IC50 values were 44.49 and 67.78 µg/mL, respectively, against the tested free radicals. The oils was also potent, inhibiting the α-glucosidase (IC50 5.45 ± 0.42 µg/mL) enzyme compared to the standard. Anti-glucosidase potential was visualized through molecular docking simulations where ten compounds of the oil were found to be the leading inhibitors of the selected enzyme based on interactions, binding energy, and binding affinity. The oil was found to be an effective anti-inflammatory (61%) agent compared with diclofenac sodium (70.92%) via the carrageenan-induced assay. An appreciable (48.28%) analgesic activity in correlation with the standard aspirin was observed through the acetic acid-induced writhing bioassay. The oil from the n-hexane fraction of S. edelbergii contained valuable bioactive constituents that can act as in vitro biological and in vivo pharmacological agents. However, further studies are needed to uncover individual responsible compounds of the observed biological potentials which would be helpful in devising novel drugs

Synthesis and Characterization of Acrylamide/Acrylic Acid Co-Polymers and Glutaraldehyde Crosslinked pH-Sensitive Hydrogels

This project aims to synthesize and characterize the pH-sensitive controlled release of 5-fluorouracil (5-FU) loaded hydrogels (5-FULH) by polymerization of acrylamide (AM) and acrylic acid (AA) in the presence of glutaraldehyde (GA) as a crosslinker with ammonium persulphate as an initiator. The formulation&rsquo;s code is named according to acrylamide (A1, A2, A3), acrylic acid (B1, B2, B3) and glutaraldehyde (C1, C2, C3). The optimized formulations were exposed to various physicochemical tests, namely swelling, diffusion, porosity, sol gel analysis, and attenuated total reflection-Fourier transform infrared (ATR-FTIR). These 5-FULH were subjected to kinetic models for drug release data. The 5-FU were shown to be soluble in distilled water and phosphate buffer media at pH 7.4, and sparingly soluble in an acidic media at pH 1.2. The ATR-FTIR data confirmed that the 5-FU have no interaction with other ingredients. The lowest dynamic (0.98 &plusmn; 0.04% to 1.90 &plusmn; 0.03%; 1.65 &plusmn; 0.01% to 6.88 &plusmn; 0.03%) and equilibrium swelling (1.85 &plusmn; 0.01% to 6.68 &plusmn; 0.03%; 10.12 &plusmn; 0.02% to 27.89 &plusmn; 0.03%) of formulations was observed at pH 1.2, whereas the higher dynamic (4.33 &plusmn; 0.04% to 10.21 &plusmn; 0.01%) and equilibrium swelling (22.25 &plusmn; 0.03% to 55.48 &plusmn; 0.04%) was recorded at pH 7.4. These findings clearly indicated that the synthesized 5-FULH have potential swelling characteristics in pH 6.8 that will enhance the drug&rsquo;s release in the same pH medium. The porosity values of formulated 5-FULH range from 34% to 62% with different weight ratios of AM, AA, and GA. The gel fractions data showed variations ranging from 74 &plusmn; 0.4% (A1) to 94 &plusmn; 0.2% (B3). However, formulation A1 reported the highest 24 &plusmn; 0.1% and B3 the lowest 09 &plusmn; 0.3% sol fractions rate among the formulations. Around 20% drug release from the 5-FULH was found at 1 h in an acidic media (pH1.2), whereas &gt;65% of drug release (pH7.4) was observed at around 25 h. These findings concluded that GA crosslinked 5-FU loaded AM and AA based hydrogels would be a potential pH-sensitive oral controlled colon drug delivery carrier

The ameliorative effects of ceftriaxone and vitamin E against cisplatin-induced nephrotoxicity

International audienceNephrotoxicity is a common adverse effect of treatment with cisplatin (CDDP). This study was performed to evaluate the antioxidant and nephroprotective efficacy of ceftriaxone (CTX) and vitamin E (Vit.E), alone and in combination against CDDP-induced acute renal injury. Fifty-six male albino rats were equally divided into seven groups, receiving (I) normal saline, (II) CTX (100 mg/kg, intraperitoneal [i.p] injection), (III) Vit.E (100 mg/kg orally), (IV) CDDP (5 mg/kg i.p injection), (V) CDDP plus CTX, (VI) CDDP plus Vit.E, and (VII) CDDP plus CTX in combination with Vit.E. All treatments were administered daily for 10 days except CDDP, which was given as a single dose at the sixth day of the study. Compared to normal control rats, CDDP-injected rats showed significantly (p < 0.05) higher serum levels of renal injury biomarkers (uric acid, urea, and creatinine) and tumor necrosis factor-α (TNF-α), as well as increased renal tissue concentrations of malondialdehyde, nitric oxide, and TNF-α. Moreover, CDDP administration was associated with significantly lower (p < 0.05) renal tissue levels of reduced glutathione and activities of endogenous antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) and total antioxidant capacity. All these alterations were significantly ameliorated in CDDP-injected rats, receiving CTX and/or Vit.E, compared to rats receiving CDDP alone. Interestingly, the antioxidant and anti-inflammatory effects were more marked in the CTX-Vit.E combination group, compared to groups receivingeither drug alone. In conclusion, CTX and Vit.E (especially in combination) could counteract the nephrotoxic effect of CDDP, probably through their antioxidant activities