Allicin alleviates lead-induced hematopoietic stem cell aging by up-regulating PKM2

Abstract

Hematopoietic stem cells (HSCs) aging is associated with hematopoietic dysfunction and diseases. Our previous study showed that lead exposure induced a functional decline in HSCs. Allicin, a chemical extracted from the garlic (Allium sativum L.), has been reported to have antioxidative and anti-inflammatory effects. However, the biological activities of allicin on lead-induced toxicity, especially in the hematopoietic system, remain unclear. Here, we found that lead exposure elicited aging phenotypes in HSCs, including perturbed cell quiescence, disabled self-renewal function and colony-forming ability, and myeloid-biased differentiation, all of which contributed to significant hematopoietic disorders in mice. Intragastric administration of allicin substantially ameliorated lead-induced HSCs aging phenotypes in vivo. Lead exposure induced a peroxide condition in HSCs leading to DNA damage, which reduced expression of the glycolytic enzyme pyruvate kinase M2 isoform (PKM2), a phenotype which was significantly ameliorated by allicin treatment. These findings suggested that allicin alleviated lead-induced HSCs aging by up-regulating PKM2 expression; thus, it could be a natural herb for preventing lead toxicity.

Antioxidative properties of Ocimum gratissimum alters Lead acetate induced oxidative damage in lymphoid tissues and hematological parameters of adult Wistar rats

“…These plant may exert similar protective mechanism of action with flaxseed isolate incorporated with lemon juice which was reported to exert protective properties on lead induced kidney and liver toxicity [ 69 ]. Antioxidants prevent lead-induced toxicity by; inactivating the activities of generated ROS at the gene level, lead ion chelating, and prevention of ROS formation in its maintenance in a redox state thus contributing to its weakness in reducing molecular oxygen [ 65 , 70 , 71 ]. Also, assessing the hazard index (HI) and hazard quotient (HQ) of Lead will shed more light in understanding the level of risk and toxicity of lead in the experiment animals so as to proffer an analysis for the mechanism of any outcomes with exposure to lead and OG [ 72 , 73 ].…”

Highly-Efficient Sulfonated UiO-66(Zr) Optical Fiber for Rapid Detection of Trace Levels of Pb2+

“…Recurring exposure to low levels of Pb creates serious health issues for infants and children such as slow development and permanent intellectual disability [ 10 , 11 ]. In addition to various sources, lead can be taken up by fishes and other aquatic organisms from water accumulating in humans tissues after consumption [ 12 ], and then resulting in neurological [ 13 ], hematopoietic [ 14 ], musculoskeletal [ 15 ], cardiac function [ 16 ] and reproductive damages [ 17 , 18 ]. Despite the detrimental properties of lead to living objects, there is yet a significant gap to efficiently and abruptly detect and characterize lead at extremely small levels in bioactive compounds [ 19 , 20 ].…”

The effects of aqueous extract of ocimum gratissimum on the cerebellum of male wistar rats challenged by lead acetate

“…This ability of OG to mitigate oxidative stress is ascribed to the antioxidative constituent of OG extract, which was shown to possess protective properties [19,37,45e49]. Antioxidants protect against LA-induced oxidative damage by deactivating free radicals at the molecular level, abrogating ROS formation and lead ion chelation [51,52]. More importantly, in OG extract, flavonoids and phenols, which are phytochemicals, exert their antioxidative potentials by chelating metal ions, scavenging, and deactivating enzyme activities that generate ROS [50].…”