D-+-Galactosamine (Synonyms: D-(+)-Galactosamine)

D-+-Galactosamine is a highly selective hepatotoxin that causes liver damage primarily through the production of free radicals and the consumption of uracil nucleotides^[1]. D-+-Galactosamine is a 6-carbon amino sugar derived from galactose that is used to induce hepatitis in the liver of rodents^[2]. D-+-Galactosamine poisoning can also lead to renal insufficiency, so renal failure is often associated with end-stage liver damage^[3].

In vitro, D-+-Galactosamine (5mM) treatment of mouse primary hepatocytes for 24h significantly induced apoptosis 2h after hepatotoxin administration, significantly increased cell necrosis 24h after administration, induced caspase-3 activation and DNA fragmentation in hepatocytes, but did not change the activity of caspase-6, -8, -9, SMases or cytochrome c release ^[4]. Treatment of rat primary hepatocytes with D-+-Galactosamine (1-40 mM) for 24 h reduced mitochondrial dehydrogenase activity and glutathione content in a dose-dependent manner, and increased the concentration of lipid peroxide MDA^[5].

In vivo, a single intraperitoneal injection of D-+-Galactosamine (500 mg/kg) in Sprague-Dawley rats caused significant damage to liver tissue, increased serum aspartate and alanine aminotransferase, γ-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase, sialic acid and uric acid levels, increased serum superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, catalase activities and lipid peroxidation values, and reduced serum and liver glutathione levels^[6]. A single intraperitoneal injection of D-+-Galactosamine (1400 mg/kg) in Wistar rats induced acute liver failure with severe parenchymal necrosis and severe lobular and periportal inflammatory infiltration in the liver^[7].

References:
[1] Endo Y, Shibazaki M, Yamaguchi K, et al. Enhancement by galactosamine of lipopolysaccharide (LPS)‐induced tumour necrosis factor production and lethality: its suppression by LPS pretreatment[J]. British journal of pharmacology, 1999, 128(1): 5-12.
[2] Saracyn M, Zdanowski R, Brytan M, et al. D-Galactosamine intoxication in experimental animals: is it only an experimental model of acute liver failure?[J]. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 2015, 21: 1469.
[3] Sinha M, Manna P, Sil P C. Amelioration of galactosamine-induced nephrotoxicity by a protein isolated from the leaves of the herb, Cajanus indicus L[J]. BMC complementary and alternative medicine, 2007, 7: 1-18.
[4] Siendones E, JIMÉNEZ‐GÓMEZ Y, Montero J L, et al. PGE1 abolishes the mitochondrial‐independent cell death pathway induced by D‐galactosamine in primary culture of rat hepatocytes[J]. Journal of gastroenterology and hepatology, 2005, 20(1): 108-116.
[5] Kučera O, Lotková H, Kanďár R, et al. The model of D-galactosamine-induced injury of rat hepatocytes in primary culture[J]. Mesenchymal stem cells isolated from the human bone marrow: Cultivation, phenotypic and changes, 2006, 49(1): 59-65.
[6] Catal T, Tunali S, Bolkent S, et al. An antioxidant combination improves histopathological alterations and biochemical parameters in D-galactosamine-induced hepatotoxicity in rats[J]. European Journal of Biology, 2017, 76(1): 14-19.
[7] Éboli L P C B, Netto A A S, Azevedo R A, et al. Evaluating the best time to intervene acute liver failure in rat models induced by d-galactosamine[J]. Acta Cirurgica Brasileira, 2016, 31(12): 783-792.