Increased survival after irradiation followed by regeneration of bone marrow stromal cells with a novel thiol-based radioprotector

Abstract

AimTo investigate the survival of laboratory rats after irradiation and to study the cellularity of their bone marrow and the multipotential mesenchymal stem cells (BM-MSCs) in groups treated with or without a new thiol-based radioprotector (GM2011)MethodsAnimals were irradiated by a Cobalt gamma source at 6.7 Gy. Treated animals were given i.p. GM2011 30 minutes before and 3 and 7 hours after irradiation. Controls consisted of sham irradiated animals without treatment and animals treated without irradiation. After 30 days post-irradiation, animals were sacrificed and bone marrow cells were prepared from isolated femurs. A colony forming unit-fibroblast (CFU-F) assay was performed to obtain the number of BM-MSCs.ResultsIn the treated group, 87% of animals survived, compared to only 30% in the non-treated irradiated group. Irradiation induced significant changes in the bone marrow of the treated rats (total bone marrow cellularity was reduced by ~ 60% – from 63 to 28 cells ×106/femur and the frequency of the CFU-F per femur by ~ 70% – from 357 to 97), however GL2011 almost completely prevented the suppressive effect observed on day 30 post-irradiation (71 cells ×106/femur and 230 CFU-F/femur).ConclusionAlthough the irradiation dosage was relatively high, GL2011 acted as a very effective new radioprotector. The recovery of the BN-MSCs and their counts support the effectiveness of the studied radioprotector.

Raman spectral analysis of the brainstem and responses of neuroglia and cytokines in whole-body gamma-irradiated rats after administration of aminothiol-based radioprotector GL2011

“…AS101 (ammonium trichloro(dioxoethylene-O-O')tellurate), a member of another class of radioprotectors and immunomodulators, was found to stimulate the production of IL-1, IL-6 and TNF-α, which underlines its role [52]. Thus, in addition to the previously published aminothiol mechanisms of radioprotection [11,15,16], here we showed with GL2011 another function, related to the manipulation of cytokine pathways.…”

“…Various mechanisms of action of these radioprotectors on cellular DNA have been proposed, such as free radical scavenging, induction of hypoxia, formation of mixed disulfides, and hydrogen and electron donation as mechanisms of free radical elimination leading to restoration of damaged cellular components [13,14]. This study is a continuation of a preclinical trial of the radioprotective effects of a newly synthesized, naturally occurring aminothiol compound, GL2011 [15,16] that acts as an antioxidant and immunostimulatory agent. Its non-toxicity to albino Wistar rats was also confirmed.…”

“…at three time points (30 min prior to irradiation, 3 h and 6 h after irradiation), GL2011 significantly reduced the mortality of whole-body irradiated animals (87% survival compared to 30% survival of unprotected animals [15]). GL2011 was shown to have a significant effect on the regeneration of intestinal epithelial microvilli [15] and bone marrow cells of irradiated animals 30 days after treatment [16]. The GL2011 radioprotector has also been shown to induce enhanced expression of proteins and antioxidant enzymes, including vimentin, septin-5, voltage-dependent anion selective channel protein and superoxide dismutase 2 [15].…”

The features of cellular composition of rat bone marrow at acute irradiation and s-heteryl modified cysteamine administration

“…показали радіозахисну дію аміфостину на гемопоетичні та мезенхімальні клітини КМ при опроміненні іn vіtro [5]. Також був вивчений радіопротекторний ефект нової сполуки тіолового ряду (GM2011) щодо збереження клоногенних МСК КМ і поліпшення показників виживання тварин при опроміненні іn vіvo у дозі 6,7 Гр [6]. Наші попередні дослідження в експериментах з тотальним опроміненням у мінімальній абсолютно летальній дозі ЛД 95/30 дали змогу виявити високу радіопротекторну активність сполуки з ряду модифікованих амінотіолів -гідрохлорид-S-(6-етокси-2-метилхінолін-4-іл)-цистеаміну -S-гетерилмодифікованого цистеаміну (S-ГМЦ).…”