Disturbances of energy metabolism in the internal organs in traumatic cranial injury on the background of diabetes

Abstract

Traumatic cranial injury is one of the leading reasons in the statistics of mortality. Modern ideas about the pathogenesis of traumatic brain injury based on the allocation of primary and secondary factors of brain damage. One of the main causes of secondary brain injury is hypoxia – insufficient provision with oxygen. Changes in oxygen balance lead to activation of oxidative stress, disturbances of mitochondria membranes and their death, and progression of energy metabolism imbalance caused by trauma. Millions of people worldwide suffer from diabetes mellitus. One of the factors that influences the development of complications of diabetes, is an accumulation of highly toxic peroxide compounds that intensify the processes of destabilization of cell membranes. Further research of peculiarities of oxidative stress and energy metabolism imbalance in diabetes associated with trauma will provide the basis for therapeutic directions to increase treatment options and improve patient health and well-being.

Therefore, the purpose of this work is to study the effect of traumatic cranial injury on the energy supplying processes in the liver and kidneys of rats with streptozotocin diabetes, as well as establishing a link between impaired mitochondrial oxidation and the intensity of oxidative stress.

Hundred adult male Wistar rats, weighing 180-220 g, were used in this study. Rats were assigned to one of four groups: (1) control animals (n=10); (2) rats with diabetes (n=10); (3) rats with closed cranial trauma (n=40); (4) animals with cranial trauma on the diabetes background (n=40). To induce diabetes, streptozotocin (“Sigma-Aldrich”,USA) was dissolved in citrate buffer (pH 4.5) and a single intra-peritoneal injection (60 mg/kg) was given to each animal. The application of the cranial injury was done according to the method developed in our laboratory. The rats were sacrificed under thiopental sodium anesthesia by total bloodletting from the heart. The rats of groups 3 and 4 were euthanized 3 h, 24 h, 5, and 14 days  after the onset of the injury. Blood of the experimental animals was analyzed for succinate dehydrogenase, cytochrome oxidase, proton adenosine triphosphatase activity, the concentration of adenosine triphosphate, diphosphate, and monophosphate. Additionally, we studied the products of protein and lipid peroxidation.

Succinate dehydrogenase activity decreased 22,6% after 3 h, by 38,8% after 24 h, by 34,7% after 5 days, and by 22,2% after 14 days post-traumatically in diabetic rats. The most pronounced decrease in cytochrome oxidase activity in the liver was 26,3 and 40 % after 5 and 14 days after TBI, respectively. These changes were accompanied by an increase in the proton adenosine triphosphatase activity in the liver by 42,1, 53,5, 68,6, 63,3 % after 3 h, 1, 5 and 14 days after injury, compared to injured rats without diabetes. Statistically significant increase in the products of protein and lipid peroxidation after traumatic cranial injury in combination with diabetes mellitus towards non-diabetic injured rats was observed.

It has been established that there are inhibition of the respiratory chain enzymes activity (succinate dehydrogenase and cytochrome oxidase), an increase in the proton adenosine triphosphatase activity and a decrease in the concentration of adenosine triphosphate in the liver and kidneys of experimental animals with cranial trauma and diabetes. The degree of mitochondrial oxidation impairment and adenosine triphosphate synthesis processes positively correlates with the intensity of oxidative stress in the liver and kidneys.  In the event of traumatic cranial injury on the background of concomitant diabetes mellitus, indicators of the mitochondrial energy supplying oxidation, the level of macroergic compounds and the intensity of oxidative stress were significantly worse compared to analogical indicators in the normoglycemic injured animals.