Abstract

Acetaminophen (APAP) is an antipyretic and analgesic drug that can be bought and used without a prescrip- tion worldwide. A dosage of APAP greater than the maximum recommended dosage can increase the risk of organ damage. Mesenchymal stem cells (MSCs) are isolated from various human tissues and used for therapy, in which beneficial effects are attributed mainly to mesenchymal stem cell-derived extracellular vesicles (MSC-EVs). However, no study has focused on the protective effect of exosomes in combination with APAP. Therefore, the present study was carried out to investigate the protective effect of taking exosomes against APAP toxicity on the fallopian tubes and uterus. Forty female Wistar albino rats (12–14 weeks old) were randomly divided into four equal groups: control, APAP (received 1 g/kg APAP), exosome (received 30 μg of exosomes), and APAP+exosome groups that received simultane- ously 1 g/kg APAP and were followed three days later by a tail vein injection 30 μg of exosomes. The uterus and fallo- pian tubes were removed for histological and immunohistochemical analyses after the animals were sacrificed. The results showed that exosomes' administration after APAP decreased APAP's autophagic effects. Moreover, exosome treatment exhibited a protective effect on the immunoreactivity intensities of autuphagy markers (Beclin-1, p62, and LC3). The treatments with exosomes had no adverse effect on the uterus or fallopian tubes. The administration of exo- somes after APAP toxicity can decrease cell death through the autophagy effect of APAP. It is suggested that this com- pound can decrease the toxic effects of APAP. Further studies are needed to evaluate the molecular mechanism of this hyperanalgesic effect.

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