Inhibition of chemotherapy‑induced apoptosis of testicular cells by squid ink polysaccharide

Abstract

The aim of this study was to determine the mechanisms driving the protective effects of squid ink polysaccharide (SIP) against cyclophosphamide (CP)-induced testicular damage, focusing on germ cells. In the testes of mice exposed to CP and/or SIP, the present study examined the levels of reactive oxygen species (ROS) and malondialdehyde, activity of superoxide dismutase levels, protein expression levels of B-cell lymphoma 2 (Bcl2), Bcl2-associated X protein (Bax), and total Caspase 3, activation of p-p38 and p-Akt proteins, and tissue morphology. The findings indicated that CP induced ROS production and oxidative stress, resulting in testicular damage. However, under administration of SIP, oxidative stress was impaired and the testicular toxicity induced by CP was weakened, which implied that SIP may have an important role in preventing chemotherapeutic damage to the male reproductive system via promoting antioxidant ability. Furthermore, the altered expression levels, including the upregulation of Bax and Caspase 3, downregulation of Bcl-2 and the increased Bax/Bcl-2 ratio, indicated that apoptosis occurred in CP exposed testes of mice; however, the alterations were reversed in mice treated with SIP. Moreover, in CP-exposed testes, p38 and Akt proteins were significantly phosphorylated (P<0.05), whereas in the testes of mice co-treated with SIP and CP, phosphorylation of the two proteins was inhibited, demonstrating that the two signalling pathways participated in the regulative processes of the deleterious effects caused by CP, and the preventive effects SIP mediated.

Octopus vulgaris ink extracts exhibit antioxidant, antimutagenic, cytoprotective, antiproliferative, and proapoptotic effects in selected human cancer cell lines

“…Moreover, a decrease of Beclin‐1 protein expression was observed due to the polysaccharide treatment. Blockade of the acrolein induced p38 MAPK and PI3K/Akt signals by glycosaminoglycans from the same ink also evaded the autophagic mechanism (Gu, Yang, Duan, et al., 2017).…”

A Potential Adjuvant Agent of Chemotherapy: Sepia Ink Polysaccharides

“…SIP has been verified to have chemoprophylactic actions on the reproductive system [ 29 , 48 , 49 , 50 , 51 , 52 , 53 ]. When male mice exposed to cyclophosphamide were administered SIP, the abnormal rates of their sperm declined, and the foetal abnormalities in female mice mated with them also declined, with total foetal count and average foetal count increasing [ 48 ].…”

“…Drug-induced oxidative stress and DNA strand breakage are two critical causes [ 60 , 61 , 62 , 63 , 64 ]. Cyclophosphamide-exposed mice/rats showed disruption of testicular antioxidant capacity and histopathologic changes through suppression of the nuclear factor erythroid 2 related factor 2 (Nrf2)/antioxidant response element (ARE) signalling pathway [ 48 , 49 , 50 , 51 , 52 , 60 , 61 , 62 ]; however, testicular functional disorders of the chemotherapeutic model animals were prevented by SIP via activation of the antioxidant signalling pathway [ 48 , 49 , 50 , 51 , 52 ]. In addition, SIP can prevent animals from cyclophosphamide-mediated mutation in vivo and H 2 O 2 /UV-induced DNA strand break in vitro [ 28 , 65 ].…”

“…In addition, SIP can prevent animals from cyclophosphamide-mediated mutation in vivo and H 2 O 2 /UV-induced DNA strand break in vitro [ 28 , 65 ]. The testicular cells of cyclophosphamide-exposed mice, including spermatogonia, Sertoli cells, and Leydig cells, were protected by SIP via repression of cyclophosphamide-induced autophagy-associated cell death and apoptosis; the mechanisms involved p38 mitogen-activated protein kinase and phosphoinositide 3-kinase PI3K)/Akt signalling pathways [ 51 , 52 , 53 ]. Similarly, for cyclophosphamide-mediated ovarian failure, SIP also successfully inhibited follicle deletion and granule cell disruption by repressing cyclophosphamide-induced autophagy-associated cell death and apoptosis via regulation of p38 mitogen-activated protein kinase and PI3K/Akt pathways, resulting in functional rescue of the ovaries of cyclophosphamide-exposed mice [ 29 ].…”

Identification of aldehyde oxidase 3 as a binding protein for squid ink polysaccharides using magnetic nanoparticles

“…Also, SIP inhibited apoptosis through repressing induction of autophagy in testis and ovary of cyclophosphamide treated mice and in mouse Leydig cells exposed acrolein, a metabolite of cyclophosphamide. [5][6][7][8] These results indicate cancer chemoprevention property of the natural marine polysaccharides.…”