Triethylenetetramine reduces some blood parameters in alloxan-induced diabetes mellitus in New Zealand white rabbit: evidence for histopathologic effects

Diabetes mellitus (DM) belongs to one of the metabolic diseases which is completely characterized with insulin deficiency, resistance to the action of insulin, and/or both items (1). DM is known to involve the significant manifestations not only for premature atherosclerosis and renal disease but also for their rapid progression. Indeed, those complications are the substantial cause of death in DM, wherein chronic cardiovascular and renal complications and hyperglycemia are main adjectives (2). In addition, DM is associated with a series of metabolic alterations in which Cu accumulation and tissue imbalance of Cu are occurred in the extracellular matrix. Copper (Cu) as unbounded form, strongly possesses pro-oxidant feature in mammalian tissues and may trigger pathways that activates excessive generation of reactive oxygen species (ROS), such as the superoxide anion or hydroxyl radical (3) and their levels may elevate under pathological conditions and cause tissue damage (4). Macroangiopathy, microangiopathy, hypercholesterolemia, and hypertension in diabetic subjects are well associated with elevated serum Cu concentration (5). TETA (trientine) belongs to structure analog of linear polyamine compounds (spermidine and spermine) (5) Abstract This study aimed to assess whether the triethylenetetramine (TETA) is impressed the plasma level of homocysteine (Hcy), total sialic acid (TSA) and cardiac troponin I (cTnI) as cardiovascular diseases risk factors, cystatin c (Cys c) and glucose along with histopathologic changes in alloxan induced diabetes mellitus in rabbit. Twenty number New Zealand white rabbits were assigned for this study. After induction of diabetes mellitus, TETA was orally administrated with different doses (10, 20, 40 mg/kg/day, A, B, C groups respectively) for 6 months daily and group D (as positive control) not received TETA. In the following, above parameters, insulin and glucose were measured in the all groups. Furthermore, histopathologic evaluation was carried out for aorta, kidney and pancreas in the all ones. Amounts of plasma cTnI, Hcy, TSA, Cys c and glucose concentrations decreased significantly (P < 0.01) in group C (40 mg/kg/day) compared with group D (positive control). In respect of insulin, normalizing of insulin occurred in group C (40 mg/kg/day) compared with group D (positive control). It is worth mentioning that during increasing of TETA dose, those levels decreased. In terms of histopathology, ameliorative and restoring effect of TETA on pancreatic beta-cells, glomeruli, renal tubules and aorta was determined in this study. The results suggested that TETA administration plays substantial role in tremendous alleviation of forenamed parameters and amelioration of beta-cells, renal glomeruli and tubules. Hence, TETA in the dose 40 mg/kg/day may utilize in the part of human diabetes mellitus management including cardiovascular, renal diseases and glucose normalizing.