Almost 90% of diabetes mellitus cases worldwide are diabetes type 2. Among the diabetes-related complications,　the bladder function is also negatively affected. In the present study we investigated the oxidative stress-related alterations in the bladder in the early stage of the disease. Additionally, animals were treated with antioxidants to evaluate their effects on the histology of the bladder.

By a single dose of streptozotocin (40mg/kg) intraperitoneally (i.p.) diabetes was induced in 8-week-old male Wistar rats. Two days later diabetes was confirmed by measuring urinary glucose and the next day the diabetic animals were randomly separated into 3 groups and fed for 14 days with a high fat diet (60% of the calories were from fat). Among the three diabetic groups, one group received no treatment (DM group), another group received orally resveratrol (10mg/Kg; Resv group) and the third one received taurine i.p. (1g/Kg; Tau group). Age matched control animals were used and fed with normal diet (Control group). At the completion of the 14-day-experimental period, the animals were sacrificed and the bladders were processed for histological evaluation, measurements of malondialdehyde (MDA) and immunohistochemistry (IHC) for oxidative stress markers. Blood samples were also collected.

Two weeks of diabetes significantly decreased the body weight in all the diabetic animals compared to the Control group. Furthermore, serum glucose levels were significantly higher in diabetic groups. Antioxidants administration had no significant effect in hyperglycemia. DM group demonstrated significantly higher ratio of bladder weight to body weight compared to the Control. Histological evaluation of the bladder demonstrated mild damage of the tissue in the DM group such as abruption of the mucosa from the muscularis as well as edema in the transitional epithelium. All these alterations were not observed in the treatment groups. The DM group demonstrated significantly higher levels of MDA in the bladder compared with Control, Resv or Tau group. Fourteen days of diabetes without treatment in the DM group induced moderate to strong expression of oxidative stress marker MDA, 4-Hydroxynonenal and DNA oxidative stress marker 8-deoxyguanosine compared with the other three groups. In the DM group these oxidative stress markers were localized in the transitional epithelium, the mucosa as well as the muscular area.

In the early stage of the disease, the histological alterations that are induced by the diabetes appear to be mild. On the other hand, the oxidative stress at this stage is highly expressed and present in the bladder. Therefore, it is possible to reverse the damage in the bladder tissue once it is treated appropriately and on time. Our results indicate that both resveratrol and taurine had a beneficial effect in the histological changes induced by the diabetes; hence antioxidant treatment may be of value for diabetic patients. Additionally, lipid peroxidation levels as evaluated by the concentration of MDA in the bladder as well as the expression and localization of oxidative stress markers and DNA oxidative damage in the bladder were significantly decreased by the resveratrol or taurine treatment compared to the no treated diabetic group. This further gives evidence that the diabetes-induced oxidative stress in the bladder is highly connected to the histological alterations in the bladder. Consequently, downregulation of oxidative stress levels can result in the improvement of bladder histology. Antioxidants could not treat hyperglycemia, which means that antioxidants cannot replace the anti-diabetic medication but mostly work as a supplementary therapy for diabetes-induced bladder dysfunction.

The prompt diagnosis of diabetes can be crucial for the progression of the disease. Specifically in the bladder, it appears that both mild damage in structural level, as well as oxidative damage in molecular level can be prevented by resveratrol or taurine treatment.