L. Leaf Extract Dose-Dependently Modulates Oxidative Stress in the Kidney and Exerts Anti-Fibrotic and Anti-Inflammatory Properties by the Molecular Mechanisms Independent of NRF-2 Signalization Mirroring the Effects of Losartan in SHR.

Previously, we confirmed systemic antihypertensive and antioxidant properties of L. leaf extract (UE) in spontaneously hypertensive rats (SHR). Here, we aimed to evaluate whether UE can alter the NO and Nrf-2 signaling to prevent local oxidative stress and kidney damage in the model of essential hypertension. SHR were divided into five groups: SHRC-control, received 0.5 mL/day of water, SHR+L received 10 mg/kg/day of losartan, SHR+UE10, SHR+UE50, and SHR+UE200 received 10, 50, and 200 mg/kg/day during next 4 weeks. At the end of the experiment, urine samples were collected for albuminuria and nitrate/nitrite assessment. Mean arterial pressure (MAP) was measured, and blood samples were collected for plasma creatinine evaluation. Kidneys were analyzed for nitrate/nitrite, oxidative stress, and target molecules by biochemical, Western blot, and immunofluorescent techniques. Losartan and UE50 significantly reduced MAP, albuminuria, oxidative stress, fibroinflammatory markers, and NRF-2/CAT/SOD signaling, with a significant increase in 6-nitrotryptophan and eNOS expressions compared to control. The effects of UE showed dose dependence. Beneficial effects of UE and losartan were independent of NRF-2 signalization in SHR. Interestingly, all treatments induced the increase in 6-nitrotryptophan expression, thus further studies are needed to elucidate the mechanisms of such nitrated tryptophan.