Silymarin protects against renal injury through normalization of lipid metabolism and mitochondrial biogenesis in high fat-fed mice. Bin Feng ,Meng Ran,Bin Huang ,Bi Yan,Shen Shanmei,Zhu Dalong Free radical biology & medicine Obesity is associated with an increased risk of chronic kidney diseases and the conventional treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors is not enough to prevent renal injury and prolong the progression of disease. Recently, silymarin has shown protective effects on renal tissue injury, but the underlying mechanisms remain elusive. The goal of this study was to investigate the potential capacity of silymarin to prevent renal injury during obesity induced by high fat diet (HFD) in mice. In vivo, male C57BL/6 mice received HFD (60% of total calories) for 12 weeks, randomized and treated orally with vehicle saline or silymarin (30mg/kg body weight/d) for 4 weeks. In vitro, human proximal tubular epithelial cells (HK2) were exposed to 300μM palmitic acid (PA) for 36h followed by silymarin administration at different concentrations. The administration of silymarin significantly ameliorated HFD induced glucose metabolic disorders, oxidative stress and pathological alterations in the kidney. Silymarin significantly mitigated renal lipid accumulation, fatty acid β-oxidation and mitochondrial biogenesis in HFD mice and PA treated HK2 cells. Furthermore, silymarin partly restored mitochondrial membrane potential of HK2 cells after PA exposure. In conclusion, silymarin can improve oxidative stress and preserve mitochondrial dysfunction in the kidney, potentially via preventing accumulation of renal lipids and fatty acid β-oxidation. 10.1016/j.freeradbiomed.2017.06.009

Amelioration of silymarin against cadmium-induced toxicity in pregnant rats and their fetuses. Birth defects research BACKGROUND:Silymarin is an antioxidant without side effects even at relatively high physiological dosage. Therefore, it is safely used as a herbal medicine for treating different diseases. AIM OF WORK:The purpose of this study was to examine the toxicity of cadmium (Cd) in pregnant rats and their fetuses and the ameliorative effects of silymarin (SL) against this toxicity. MATERIALS & METHODS:A total of 24 pregnant rats allocated into four equal groups. Control, silymarin (200 mg/kg), Cd (5 mg/kg), and a combination of Cd and silymarin concurrent from 6 to 20th gestational day. Number of corpora lutea, dams', gravid uteri, placental weights, and likewise fetal body weights and lengths were analyzed as physical parameters. Serum levels of aspartate transaminase, alanine transaminase, creatinine, urea, uric acid, and maternal and fetal liver tissues for malondialdehyde, superoxide dismutase, catalase and glutathione activity were studied. The histology of hepatic and renal tissues for both mothers and fetuses was examined. Data were statistically analyzed by analysis of variance test and Duncan's multiple range test was used to compare group means. RESULTS:The findings evidenced that Cd causes teratogenic abnormalities and histopathological variation in hepatic and renal tissues of both mothers and fetuses. Cd triggers oxidative stress and disrupts liver and kidney function. In Cd + silymarin treated rats exhibited improvement in the pregnancy outcomes, reduced histopathological changes, oxidative stress as well as liver and kidney enzymes. CONCLUSION:We deduced that using of silymarin during gestation is effective and ameliorate the toxic maternal complications caused by cadmium. 10.1002/bdr2.2217

Silymarin pretreatment protects against ethanol-induced memory impairment: Biochemical and histopathological evidence. Journal of chemical neuroanatomy BACKGROUND:Ethanol (Eth.) abuse induces memory impairment. Oxidative damage and apoptosis are considered the likely causes of memory impairment. Silymarin (Sil.) is a flavonoid isolated from the plant Silymarin marianum (milk thistle). While studies have reported the neuroprotective effect of Sil. against neurodegenerative processes, the precise mechanism of action of Sil. in Eth.-induced memory impairment remains unclear. METHODS:Twenty-eight rats were equally divided into four groups: Control (saline 1 ml/rat); Sil. (200 mg/kg for 30 days); Eth. (2 g/kg/day for 30 days); and Sil. + Eth. Behavioral tests including inhibitory avoidance and open field were used to investigate memory and locomotion. Brain antioxidant parameters, including catalase, superoxide dismutase, total antioxidant capacity and total thiol group, plus oxidative parameters, including malondialdehyde and total oxidant status, followed by hippocampal apoptosis (Bax/Bcl2, cleaved caspase) and histopathological changes were evaluated in the groups. RESULTS:While the administration of Eth. impaired memory, Sil. significantly reversed Eth-induced memory deficits. Eth. administration also augmented brain oxidative and hippocampal apoptosis parameters. In contrast, a marked reduction in brain antioxidant and anti-apoptotic parameters was observed in the Eth. group. At the tissue level, hippocampal sections from Eth.-treated animals revealed severe neuronal damage. The administration of Sil. to Eth.-treated rats remarkably alleviated all the said Eth.-induced biochemical and histopathological effects. On the contrary, Sil. alone did not change the behavior and biochemical/molecular parameters. CONCLUSION:The memory-enhancing effect of Sil. in Eth.-induced demented rats may be partly mediated by the augmented antioxidant effects and amelioration of apoptotic and histopathological changes. 10.1016/j.jchemneu.2023.102310

Silymarin protects against radiocontrast-induced nephropathy in mice. Life sciences Silymarin, an extract from Silybum marianum (milk thistle) containing a standardized mixture of flavonolignans that ameliorates some types of liver disease and, more recently, kidney damage, could be used for the ROS-scavenging effect of these antioxidants. Furthermore, contrast-induced nephropathy (CIN) is an iatrogenic impairment of renal function in patients subjected to angiographic procedures for which there is not yet a successful preventative treatment. Recent evidence has shown that this event is related to tubular/vascular injury activated mainly by oxidative stress. However, whether this bioavailable and pharmacologically safe extract protects against CIN is not clear. We proposed to evaluate the possible protective role of the antioxidant silymarin in an experimental model of CIN. Adult male Swiss mice were separated into 6 groups and pretreated orally with silymarin (50, 200 and 300 mg/kg), N-acetylcysteine (200 mg/kg) or vehicle for 5 days before the CIN and control groups. Renal function was analyzed by plasma creatinine, urea and cystatin C levels. Additionally, blood reactive oxygen species (ROS) were evaluated using ROS bioavailability, protein oxidation and DNA damage. Renal oxidative damage was evaluated using apoptosis/cell viability assays and histological analysis. We showed that silymarin preserved renal function and decreased systemic and renal oxidative damage (antigenotoxic and antiapoptotic properties, respectively) in a dose-dependent manner and was superior to conventional treatment with N-acetylcysteine. Histologically, silymarin treatment also had beneficial effects on renal glomerular and tubular injuries. Therefore, silymarin prophylaxis may be an interesting strategy for the prevention of CIN. 10.1016/j.lfs.2019.04.061

Silymarin protects the rats against paraquat-induced acute kidney injury via Nrf2. Jia C,Zhang Z,Wang J,Nie Z Human & experimental toxicology BACKGROUND:Paraquat (PQ) poisoning induces severe acute kidney injury and causes extremely high rate of death. In this study, we aimed to investigate the protective effects of silymarin on PQ-induced acute kidney injury and explore the underlying mechanisms. METHODS:A rat model was established through intraperitoneal injection of PQ. Rats were administrated with saline or silymarin for 3 days. Then, survival rate, physiological parameters, and renal injury score were evaluated. The apoptosis and oxidative stress in kidney tissues were determined through hematoxylin and eosin staining, quantitative reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assays. RESULTS:Silymarin administration could significantly increase the survival rate of PQ-poisoned rats. It was found that silymarin treatment improved renal function, decreased injury score in kidney tissues, and inhibited the apoptosis and oxidative stress in PQ-induced acute kidney injury through the activating the signaling pathway of Nrf2 and promoting its nuclear translocation. CONCLUSION:Silymarin exhibited a protective effect against PQ-induced kidney injury, suggesting that treatment with this flavonoid could be a potential therapeutic agent for the treatment of acute kidney injury. 10.1177/09603271221074334