Piperine Enhances the Antioxidant and Anti-Inflammatory Activities of Thymoquinone against Microcystin-LR-Induced Hepatotoxicity and Neurotoxicity in Mice

Abstract

Microcystin- (MC-) LR is the most frequent cyanotoxin produced by Microcystis aeruginosa cyanobacteria in the contaminated freshwater environment. MC represents a health hazard to humans and animals. Therefore, the present study was designed to evaluate the potential ameliorative effect of thymoquinone (TQ) and/or piperine (PP) against MC toxicity in mice. Fifty-six mice were randomly divided into seven experimental groups. Group I is the normal control that received distilled water for 21 days; Group II (TQ) was treated with TQ (10 mg/kg, i.p) for 21 days; Group III (PP) was treated with PP (25 mg/kg, i.p) for 21 days; Group IV (MC) was treated with MC (10 μg/kg, i.p) for 14 days and served as the toxic control; and Groups V, VI, and VII received TQ and/or PP 7 days prior to MC and continued for 14 days with MC. The results revealed that MC elicited hepatotoxicity and neurotoxicity which was evident due to the significant elevation of serum AST, ALT, γGT, ALP, LDH, IL-1β, IL-6, and TNF-α levels. Furthermore, MC markedly increased MDA and NO contents along with reduction of GSH, SOD, CAT, and GSH-Px in liver and brain tissues. The electron transport chain may be a possible target for MC. TQ and/or PP ameliorated the MC-mediated oxidative damage in the liver and brain which might be attributed to their antioxidant properties. However, the concurrent treatment of TQ and PP showed the best regimen as a result of the PP-enhanced bioavailability of TQ.

Coenzyme Q10 supplementation mitigates piroxicam-induced oxidative injury and apoptotic pathways in the stomach, liver, and kidney

“…Oxidative stress is a process that is initiated through well-known ROS (superoxide anion, O2 • − ; hydrogen peroxide, H 2 O 2 ; hydroxyl radical, OH • ) and reactive nitrogen species, RNS (nitric oxide, NO and peroxynitrite, ONOO − ), which are up-regulated due to exhaustion of endogenous antioxidant molecules. Subsequently, tissue damage is elicited by several mechanisms, including the promotion of lipid peroxidation (LPO), mitochondrial perturbation, DNA damage, protein nitration, and apoptotic cell death [ [36] , [37] , [38] , [39] , [40] ].…”

“…It is well known that considerable quantities of OH • are produced from H 2 O 2 (by Fenton's reaction) when CAT is depleted [ 41 ]. OH • is the most harmful radical among ROS because it causes membrane damage by direct breaking down the membrane lipid content and initiating LPO and producing MDA [ 11 , 36 , 42 ]. This process was confirmed in the present study by the dramatic increase in MDA in the liver and kidney, which confirmed the occurrence of membrane damage.…”

Thymoquinone, as a Novel Therapeutic Candidate of Cancers

“…TQ–piperin combination has reduced the inflammation resulting from microcystin in mice, lowering inflammatory markers (IL-1β, IL-6 and TNF-α) in the serum. The TQ–piperin combination has also decreased the oxidative damage triggered by microcystin in liver tissue and reduced malondialdehyde (MDA) and NO, while inducing glutathione (GSH) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities [ 128 ]. Furthermore, TQ could reduce LPS-mediated inflammatory cytokine secretion, monocyte recruitment factors, and monocyte in human endothelial (HECV) cell lines.…”

Thymoquinone loaded calcium alginate and polyvinyl alcohol carrier inhibits the 7,12‐dimethylbenz[a]anthracene‐induced hamster oral cancer via the down‐regulation of PI3K/AKT/mTOR signaling pathways

“…Thymoquinone (TQ) is an 2‐methyl‐5‐isopropyl‐1, 4‐benzoquinone, which is major found in Nagalla sativa (Black cumin seed and oils) 11 . In particular, TQ are recognized to possesses a wide range of medicinal values such as anticancer, immunomodulatory, 12 antioxidant, 13 antidiabetic, 14 antiinflammatory, 15 analgesic, 16 antihypertensive, 17 gastro‐protective, 18 renal protective, 19 and anticancer 20 . Other such as derivatives from this dithyoquinone, TQ and thymol 21 .…”