Luteolin mitigates potassium dichromate‐induced nephrotoxicity, cardiotoxicity and genotoxicity through modulation of Kim‐1/Nrf2 signaling pathways

Abstract

Environmental and occupational exposure to chromium compounds has become potential aetiologic agent for kidney disease with excessive generation of free radicals, apoptosis, and inflammatory. These pathophysiologic mechanisms of potassium dichromate (K2Cr2O7) have been well correlated with nephrotoxicity and cardiotoxicity. The cardioprotective and nephroprotective effects of Luteolin, a known potent antioxidant were evaluated in this study with 40 healthy rats in four experimental groups: Group A (normal saline), Groups B (30 mg/kg K2Cr2O7), Group C (Luteolin 100 mg/kg and K2Cr2O7 30 mg/kg), and Group D (Luteolin 200 mg/kg and K2Cr2O7 30 mg/kg), respectively. Markers of antioxidant defense system, oxidative stress, blood pressure and micronucleated polychromatic erythrocytes (MnPEs), immunohistochemistry of Kidney, injury molecule (Kim‐1), nuclear factor erythroid 2‐related factor 2 (Nrf2), and cardiac troponin I were determined. Administration of K2Cr2O7 increased blood pressure parameters in systolic, diastolic and mean arterial blood pressures, markers of oxidative stress, and frequency of micronucleated polychromatic erythrocytes, together with reduction in serum nitric oxide level. Renal Kim‐1 and cardiac troponin I expressions were higher, but lower expressions of renal and cardiac Nrf2 were recorded with immunohistochemical analysis. Pre‐treatment with Luteolin restored blood pressure parameters, with concomitant reduction in oxidative stress indicators, augmented antioxidant mechanisms and serum Nitric oxide level, lowered the expressions of Kim‐1, cardiac troponin I and up‐regulated of both cardiac and renal Nrf2, reduced the frequency of micronucleated polychromatic erythrocytes. Taken together, this study therefore demonstrates the cardioprotective, nephro protective and antigenotoxic effects of Luteolin through antioxidantive and radical scavenging mechanisms.

Selenium regulates Nrf2 signaling to prevent hepatotoxicity induced by hexavalent chromium in broilers

“…There were studies have demonstrated that Cr(Ⅵ) exposure could lead the downregulation of mRNA and protein expressions of Nrf2, NQO1, and HO-1 in a dose dependent manner ( Yang et al, 2021 ). However, antioxidants enhanced Nrf2 mediated antioxidant defense system to prevent Cr(Ⅵ)-induced cardiotoxicity, pulmonary toxicity, and nephrotoxicity in rats ( Lv et al, 2020 ; Awoyomi et al, 2021 ). Se, as a powerful antioxidant, has been shown to reduce the toxic damage caused by As or Cd by activating the Nrf2 pathway ( Zwolak, 2020 ).…”

Renoprotective Effects of Luteolin: Therapeutic Potential for COVID-19-Associated Acute Kidney Injuries

“…Additionally, luteolin inhibited the reduction in Nfe212 and Homx1 mRNA expression in Pb-treated rats, and reduced the production of proinflammatory markers (TNF-α, IL-1β and NO) and apoptotic related proteins while upregulating the expression of antiapoptotic proteins [ 136 ]. Awoyomi et al [ 137 ] showed that the pre-treatment with Luteolin (100 and 200 mg/kg) reduced acute kidney injuries induced by potassium dichromate (K 2 Cr 2 O 7 ), at dose of 30 mg/kg, through anti-oxidantive and radical scavenging mechanisms. Luteolin reduced oxidative stress indicators, augmented anti-oxidant mechanisms and serum Nitric oxide level, lowered the expressions of injury molecule (Kim-1) and up-regulated the renal, nuclear factor erythroid 2-related factor 2 (Nrf2) [ 137 ].…”

“…Awoyomi et al [ 137 ] showed that the pre-treatment with Luteolin (100 and 200 mg/kg) reduced acute kidney injuries induced by potassium dichromate (K 2 Cr 2 O 7 ), at dose of 30 mg/kg, through anti-oxidantive and radical scavenging mechanisms. Luteolin reduced oxidative stress indicators, augmented anti-oxidant mechanisms and serum Nitric oxide level, lowered the expressions of injury molecule (Kim-1) and up-regulated the renal, nuclear factor erythroid 2-related factor 2 (Nrf2) [ 137 ].…”

Phytochemicals, Biological Activities, Molecular Mechanisms, and Future Prospects of Plantago asiatica L.

“…The ability to scavenge free radicals may be one of the mechanisms of P. asiatica as a health food and traditional Chinese medicine, especially in its protective effect on various organs. Luteolin ( 2 ) scavenges free radicals to exert cardioprotective, nephroprotective, hepatoprotective, neuroprotective, and antigenotoxic effects. − Polysaccharides from P. asiatica inhibit the production of superoxide, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and hydroxyl radicals . In addition, acteoside ( 27 ) and isoacteoside ( 28 ) also can scavenge intracellular reactive oxygen species (ROS), peroxynitrite (ONOO – ), and DPPH free radicals to prevent lipid peroxidation. ,, Except for changes in ROS levels, apigenin ( 1 ) has not been found and reported on free radicals, so apigenin ( 1 ) is an antioxidant mainly through the regulation of oxidative enzyme activity.…”

“…Apigenin ( 1 ) acts as an antioxidant drug against the accumulation of ROS upon injury via the Nrf2 signaling pathway . Nrf2 signaling also mediates luteolin ( 2 ) to significantly improve oxidative stress and various tissue injuries, including heart, kidney, , liver, , brain, retina, arthrosis, ovary, and testis injuries . Furthermore, plantamajoside ( 25 ), acteoside ( 27 ), and isoacteoside ( 28 ) inhibit ROS in cells attributed to the activation of Nrf2 transcription, , as well as the increase of HO-1 expression and enzymatic antioxidants (SOD, CAT, GSH-Px, etc.)…”