The hepatorenal protective effects of silymarin in cancer patients receiving chemotherapy: a randomized, placebo-controlled trial.

BACKGROUND: Breast cancer is one of the most common diseases globally that may have side effects on liver and renal function. Pharmacological treatments to reduce adverse liver and renal effects are still limited. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the hepatorenal protective efficacy of silymarin supplementation in cancer patients receiving chemotherapy in an outpatient setting. METHOD: This is a randomized, placebo-controlled clinical trial that recruited female breast cancer patients. Participants were randomly assigned to one placebo group and two intervention groups. The control group received 140 mg of placebo daily, while the two intervention groups received 140 mg silymarin daily. Follow-up assessments were conducted at baseline, 3 weeks, and 6 weeks. At the beginning of the study, the patients were subjected to a computed tomography (CT) scan, and the liver and renal parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, Blood urea nitrogen (BUN) and Creatinine (Cr) were examined through laboratory tests. RESULTS: Despite two deaths and three dropouts, 100 patients completed the study. Silymarin showed significant effects on liver enzymes in the levels of ALP and bilirubin (P < 0.05), with no significant impact on renal function in the levels of Blood urea nitrogen (BUN) and Creatinine (Cr) (P > 0.05). The medication was well-tolerated, with minimal reported side effects (P > 0.05). DISCUSSION: The study suggests that silymarin may have hepato-renal protective potential in breast cancer patients and improve patient tolerance to chemotherapy. The data presented on the efficacy and safety of silymarin may provide stronger foundation for further trials and for a possible use in clinical practice. TRIAL REGISTRATION INFORMATION: Registration Number: IRCT20201123049474N2, First Trial Registration: 16/08/2021, Access: https://www.irct.behdasht.gov.ir/trial/57641.

Novel microwave assisted carboxymethyl-graphene oxide and its hepatoprotective activity.

This study reports a novel, eco-friendly; fast and cost-effective microwave method for synthesizing carboxymethylated graphene oxide (CMGO) from sugarcane residues. Fourier-transform infrared spectroscopy (FTIR) confirmed successful CMGO synthesis through the presence of characteristic peaks at 1567.93 and 1639.29 cm-1 (COONa vibrations) and increased CH2 intensity compared to unmodified graphene oxide (GO). Furthermore, CMGO derived from sugarcane residues demonstrated potential in mitigating the side effects of toxic materials like carbon tetrachloride (CCl4). Treatment with CMGO partially reduced elevated levels of liver enzymes (ALT and AST) and nitrogenous waste products (urea and uric acid) in CCl4-induced liver damage models, suggesting an improvement in liver function despite ongoing cellular damage.This work paves the way for a sustainable and economical approach to produce functionalized graphene oxide with promising biomedical applications in alleviating toxin-induced liver injury.

An Insight into Different Experimental Models used for Hepatoprotective Studies: A Review.

Numerous factors, including exposure to harmful substances, drinking too much alcohol, contracting certain hepatitis serotypes, and using specific medicines, contribute to the development of liver illnesses. Lipid peroxidation and other forms of oxidative stress are the main mechanisms by which hepatotoxic substances harm liver cells. Pathological changes in the liver include a rise in the levels of blood serum, a decrease in antioxidant enzymes, as well as the formation of free radical radicals. It is necessary to find pharmaceutical alternatives to treat liver diseases to increase their efficacy and decrease their toxicity. For the development of new therapeutic medications, a greater knowledge of primary mechanisms is required. In order to mimic human liver diseases, animal models are developed. Animal models have been used for several decades to study the pathogenesis of liver disorders and related toxicities. For many years, animal models have been utilized to investigate the pathophysiology of liver illness and associated toxicity. The animal models are created to imitate human hepatic disorders. This review enlisted numerous hepatic damage in vitro and in vivo models using various toxicants, their probable biochemical pathways and numerous metabolic pathways via oxidative stressors, different serum biomarkers enzymes are discussed, which will help to identify the most accurate and suitable model to test any plant preparations to check and evaluate their hepatoprotective properties.

Natural polysaccharides as promising reno-protective agents for the treatment of various kidney injury.

Renal injury, a prevalent clinical outcome with multifactorial etiology, imposes a substantial burden on society. Currently, there remains a lack of effective management and treatments. Extensive research has emphasized the diverse biological effects of natural polysaccharides, which exhibit promising potential for mitigating renal damage. This review commences with the pathogenesis of four common renal diseases and the shared mechanisms underlying renal injury. The renoprotective roles of polysaccharides in vivo and in vitro are summarized in the following five aspects: anti-oxidative stress effects, anti-apoptotic effects, anti-inflammatory effects, anti-fibrotic effects, and gut modulatory effects. Furthermore, we explore the structure-activity relationship and bioavailability of polysaccharides in relation to renal injury, as well as investigate their utility as biomaterials for alleviating renal injury. The clinical experiments of polysaccharides applied to patients with chronic kidney disease are also reviewed. Broadly, this review provides a comprehensive perspective on the research direction of natural polysaccharides in the context of renal injury, with the primary aim to serve as a reference for the clinical development of polysaccharides as pharmaceuticals and prebiotics for the treatment of kidney diseases.

The protective effect of karanjin against sepsis-induced acute lung injury in mice is involved in the suppression of the TLR4 pathway.

Sepsis-induced acute lung injury (ALI) is a severe complication of sepsis. Karanjin, a natural flavonoid compound, has been proved to have anti-inflammatory function, but its role in sepsis-stimulated ALI is uncertain. Herein, the effect of karanjin on sepsis-stimulated ALI was investigated. We built a mouse model of lipopolysaccharide (LPS)-stimulated ALI. The histopathological morphology of lung tissues was scrutinized by hematoxylin-eosin (H&E) staining. The lung injury score and lung wet/dry weight ratio were detected. The myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were scrutinized by commercial kits. Murine alveolar lung epithelial (MLE-12) cells were treated with LPS to mimic a cellular model of ALI. The cell viability was scrutinized by the CCK-8 assay. The contents of proinflammatory cytokines were scrutinized by qRT-PCR and ELISA. The TLR4 and MyD88 contents were scrutinized by qRT-PCR and western blotting. Results showed that karanjin alleviated LPS-stimulated ALI in mice by inhibiting lung tissue lesions, edema, and oxidative stress. Moreover, karanjin inhibited LPS-stimulated inflammation and TLR4 pathway activation in mice. However, treatment with GSK1795091, an agonist of TLR4, attenuated the effects of karanjin on LPS-induced ALI. Furthermore, karanjin repressed LPS-stimulated inflammatory response and TLR4 pathway activation in MLE-12 cells. Overexpression of TLR4 attenuated karanjin effects on LPS-stimulated inflammatory responses in MLE-12 cells. In conclusion, karanjin repressed sepsis-stimulated ALI in mice by suppressing the TLR4 pathway.

Sitagliptin exhibits protective effects against methotrexate-induced testicular toxicity: The involvement of oxidative stress-related factors.

Methotrexate (MTX) is widely prescribed to treat different malignancies as well as autoimmune diseases. However, it causes a range of side effects in different organs such as testis. This study aims to clarify the role of dipeptidyl peptidase 4 (DPP4) in MTX-induced testicular damage via pathways involved in oxidative stress and evaluates the protective effects of sitagliptin as a DPP4 inhibitor. Twenty-four animals randomly allocated into four groups including: (I) control, (II) MTX (20 mg/kg, i.p.), (III) sitagliptin (20 mg/kg, i.p., for four consecutive days), and MTX + sitagliptin in which received chemicals resembling group II and III. Histopathological examinations conducted to assess the structural changes in testes of different experimental groups. Also, ELISA method employed to investigate the levels of DPP4, AKT, p-AKT, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). In addition, the total malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) were assessed. The results indicated that MTX administration was accompanied with testicular damage, which reversed by sitagliptin treatment. The biochemical observations demonstrated that MTX markedly increased the levels of DPP4, decreased p-AKT/AKT ratio followed by a marked decrement in Nrf2 and HO-1 levels. Also, it was observed that MTX decreased the activity of SOD and increased total MDA content in testicular specimen. However, sitagliptin treatment diminished mentioned alterations effectively. Altogether, our findings supported the possible role of DPP4 in MTX-induced testicular toxicity along with the potential protective features of sitagliptin via suppressing of the histopathological and biochemical alterations induced by MTX.

Hepatoprotective effects of zingerone on sodium arsenite-induced hepatotoxicity in rats: Modulating the levels of caspase-3/Bax/Bcl-2, NLRP3/NF-κB/TNF-α and ATF6/IRE1/PERK/GRP78 signaling pathways.

OBJECTIVE: Long-term exposure to arsenic has been linked to several illnesses, including hypertension, diabetes, hepatic and renal diseases and cardiovascular malfunction. The aim of the current investigation was to determine whether zingerone (ZN) could shield rats against the hepatotoxicity that sodium arsenite (SA) causes. METHODS: The following five groups of thirty-five male Sprague Dawley rats were created: I) Control; received normal saline, II) ZN; received ZN, III) SA; received SA, IV) SA + ZN 25; received 10 mg/kg body weight SA + 25 mg/kg body weight ZN, and V) SA + ZN 50; received 10 mg/kg body weight SA + 50 mg/kg body weight ZN. The experiment lasted 14 days, and the rats were sacrificed on the 15th day. While oxidative stress parameters were studied by spectrophotometric method, apoptosis, inflammation and endoplasmic reticulum stress parameters were measured by RT-PCR method. RESULTS: The SA disrupted the histological architecture and integrity of the liver and enhanced oxidative damage by lowering antioxidant enzyme activity, such as those of glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) level and increasing malondialdehyde (MDA) level in the liver tissue. Additionally, SA increased the mRNA transcript levels of Bcl2 associated x (Bax), caspases (-3, -6, -9), apoptotic protease-activating factor 1 (Apaf-1), p53, tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), c-Jun NH2-terminal kinase (JNK), mitogen-activated protein kinase 14 (MAPK14), MAPK15, receptor for advanced glycation endproducts (RAGE) and nod-like receptor family pyrin domain-containing 3 (NLRP3) in the liver tissue. Also produced endoplasmic reticulum stress by raising the mRNA transcript levels of activating transcription factor 6 (ATF-6), protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and glucose-regulated protein 78 (GRP-78). These factors together led to inflammation, apoptosis, and endoplasmic reticulum stress. On the other hand, liver tissue treated with ZN at doses of 25 and 50 mg/kg showed significant improvement in oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress. CONCLUSIONS: Overall, the study's data suggest that administering ZN may be able to lessen the liver damage caused by SA toxicity.

Multimodal modulation of hepatic ischemia/reperfusion-induced injury by phytochemical agents: A mechanistic evaluation of hepatoprotective potential and safety profiles.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a clinically fundamental phenomenon that occurs through liver resection surgery, trauma, shock, and transplantation. AIMS OF THE REVIEW: This review article affords an expanded and comprehensive overview of various natural herbal ingredients that have demonstrated hepatoprotective effects against I/R injury through preclinical studies in animal models. MATERIALS AND METHODS: For the objective of this investigation, an extensive examination was carried out utilizing diverse scientific databases involving PubMed, Google Scholar, Science Direct, Egyptian Knowledge Bank (EKB), and Research Gate. The investigation was conducted based on specific identifiable terms, such as hepatic ischemia/reperfusion injury, liver resection and transplantation, cytokines, inflammation, NF-kB, interleukins, herbs, plants, natural ingredients, phenolic extract, and aqueous extract. RESULTS: Bioactive ingredients derived from ginseng, curcumin, resveratrol, epigallocatechin gallate, quercetin, lycopene, punicalagin, crocin, celastrol, andrographolide, silymarin, and others and their effects on hepatic IRI were discussed. The specific mechanisms of action, signaling pathways, and clinical relevance for attenuation of liver enzymes, cytokine production, immune cell infiltration, oxidative damage, and cell death signaling in rodent studies are analyzed in depth. Their complex molecular actions involve modulation of pathways like TLR4, NF-κB, Nrf2, Bcl-2 family proteins, and others. CONCLUSION: The natural ingredients have promising values in the protection and treatment of various chronic aggressive clinical conditions, and that need to be evaluated on humans by clinical studies.

Ethanol Extract of the Microalga Phaeodactylum tricornutum Shows Hepatoprotective Effects against Acetaminophen-Induced Acute Liver Injury in Mice.

Acute liver failure is an infrequent yet fatal condition marked by rapid liver function decline, leading to abnormalities in blood clotting and cognitive impairment among individuals without prior liver ailments. The primary reasons for liver failure are infection with hepatitis virus or overdose of certain medicines, such as acetaminophen. Phaeodactylum tricornutum (PT), a type of microalgae known as a diatom species, has been reported to contain an active ingredient with anti-inflammatory and anti-obesity effects. In this study, we evaluated the preventive and therapeutic activities of PT extract in acute liver failure. To achieve our purpose, we used two different acute liver failure models: acetaminophen- and D-GalN/LPS-induced acute liver failure. PT extract showed protective activity against acetaminophen-induced acute liver failure through attenuation of the inflammatory response. However, we failed to demonstrate the protective effects of PT against acute liver injury in the D-GalN/LPS model. Although the PT extract did not show protective activity against two different acute liver failure animal models, this study clearly demonstrates the importance of considering the differences among animal models when selecting an acute liver failure model for evaluation.

Evaluating Acetate as a Renoprotective Agent After Kidney Ischemia in a Porcine Model.

Objective: Renoprotection from reperfusion injury appears to be conferred by HIF-2a activation, which can be stimulated by exogenous acetate administration. The study objective was to assess whether administration of acetate in a porcine model can mitigate kidney injury related to ischemia-reperfusion after renal hilar occlusion. Methods: A porcine single-kidney model was created by performing a laparoscopic nephrectomy followed by animal recovery. After 2 days, the animals underwent laparoscopic hilar dissection. Block randomization was used to assign pigs into one of four experimental groups. One treatment block of pigs received 150 mEq of sodium acetate intravenously during 90 minutes of en bloc occlusion of the renal hilum (herein noted as "cross-clamping"). Another block received 0.75 g/kg of oral sodium acetate for 3 days prior to cross-clamping. A third block received no acetate and underwent hilar dissection without cross-clamping (negative control). The final block received no acetate and underwent cross-clamping (positive control). Serum creatinine was used to estimate renal function post-nephrectomy. Results: A total of 16 animals (4 pigs in each group) completed the study protocol. Median pig weight was 34.6 kg. One pig receiving IV acetate was excluded from the final analysis because of unrecoverable renal failure after cross-clamping. There was a significantly lower mean serum creatinine for the IV acetate group compared with the positive control group 72 hours after cross-clamping (p = 0.012). The same effect was not observed for the pigs receiving oral acetate. By day 7, renal function had recovered without significant difference in all groups. Conclusions: We observed that the administration of intravenous acetate conferred a significant renoprotective benefit in our single kidney ischemia-reperfusion porcine model 72 hours after hilar occlusion. This work is hypothesis-generating, and further work in human subjects undergoing renal hilar occlusion during partial nephrectomy is warranted.

Silybin prevented avermectin-induced cardiotoxicity in carp by modulating oxidative stress, inflammation, endoplasmic reticulum stress, mitochondrial apoptosis, and autophagy.

Avermectin is one of the widely used anthelmintics in aquaculture and exhibits substantial toxicity to aquatic organisms. Silybin is extensively used for its anti-inflammatory, antioxidant and anti-apoptotic biological properties. Heart is essential for the survival of fish and plays a vital role in pumping blood oxygen and nutrients. Residual avermectin in water poses harm to carp. However, there is still insufficient research on whether silybin can mitigate the toxicity of avermectin to carp heart tissues. In this research, we established a model involving carp subjected to acute avermectin exposure and administered diets containing silybin to explore the potential protective effects of silybin against avermectin-induced cardiotoxicity. The results revealed that avermectin induced oxidative stress, inflammation, endoplasmic reticulum (ER) stress, mitochondrial pathway apoptosis and autophagy in the cardiac tissues of carp. Compared with the avermectin group, silybin significantly reduced ROS accumulation in cardiac tissues, restored antioxidant enzyme activity, inhibited mRNA transcript levels of pro-inflammatory-related factors, and attenuated ER stress, mitochondrial pathway apoptosis and autophagy. Protein-protein interaction (PPI) analysis demonstrated that silybin mitigated avermectin-induced cardiac oxidative stress, inflammation, ER stress, mitochondrial pathway apoptosis and autophagy. Silybin exerted anti-inflammatory effects through the Nuclear Factor kappa B (NF-κB) pathway, antioxidant effects through the Nuclear factor erythroid 2-related factor 2 (Nrf2) - Kelch-like ECH-associated protein 1 (Keap1) pathway, alleviated cardiac ER stress through the Glucose-regulated protein 78 (GRP78)/Activating Transcription Factor 6 (ATF6)/C/EBP homologous protein (CHOP) axis, suppressed apoptosis through the mitochondrial pathway, and inhibited excessive autophagy initiation through the PTEN-induced putative kinase 1 (PINK1)/Parkin RBR E3 ubiquitin protein ligase (PARKIN) signaling pathway. This study provided evidence supporting the protective effect of silybin against avermectin-induced cardiotoxicity in carp, highlighting its potential as a dietary additive to protect fish from adverse effects caused by avermectin exposure.

Protective effects of sodium butyrate on fluorosis in rats by regulating bone homeostasis and serum metabolism.

Fluorosis due to high fluoride levels in drinking water profoundly affects the development of human skeletal and dental structures. Sodium butyrate (NaB) has been found to regulate overall bone mass and prevent pathological bone loss. However, the mechanism of NaB action on fluorosis remains unclear. In this study, a rat model of fluorosis induced by 100 mg/L sodium fluoride was used to investigate the impact of NaB on bone homeostasis and serum metabolomics. It was found that NaB significantly reduced the levels of bone resorption markers CTX-Ⅰ and TRACP-5B in fluorosis rats. Moreover, NaB increased calcium and magnesium levels in bone, while decreasing phosphorus levels. In addition, NaB improved various bone microstructure parameters, including bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone separation (Tb. SP), and structural model index (SMI) in the femur. Notably, NaB intervention also enhanced the antioxidant capacity of plasma in fluorosis rats. Furthermore, a comprehensive analysis of serum metabolomics by LC-MS revealed a significant reversal trend of seven biomarkers after the intervention of NaB. Finally, pathway enrichment analysis based on differential metabolites indicated that NaB exerted protective effects on fluorosis by modulating arginine and proline metabolic pathways. These findings suggest that NaB has a beneficial effect on fluorosis and can regulate bone homeostasis by ameliorating metabolic disorders.

Alleviation of microcystin-leucine arginine -induced hepatotoxicity: An updated overview.

OBJECTIVES: Contamination of surface waters is a major health threat for all living creatures. Some types of blue-green algae that naturally occur in fresh water, are able to produce various toxins, like Microcystins (MCs). Microcystin-leucine arginine (MC-LR) produced by Microcystis aeruginosa is the most toxic and abundant isoforms of MCs, and it causes hepatotoxicity. The present article reviews preclinical experiments examined different treatments, including herbal derivatives, dietary supplements and drugs against MC-LR hepatotoxicity. METHODS: We searched scientific databases Web of Science, Embase, Medline (PubMed), Scopus, and Google Scholar using relevant keywords to find suitable studies until November 2023. RESULTS: MC-LR through Organic anion transporting polypeptide superfamily transporters (OATPs) penetrates and accumulates in hepatocytes, and it inhibits protein phosphatases (PP1 and PP2A). Consequently, MC-LR disturbs many signaling pathways and induces oxidative stress thus damages cellular macromolecules. Some protective agents, especially plants rich in flavonoids, and natural supplements, as well as chemoprotectants were shown to diminish MC-LR hepatotoxicity. CONCLUSION: The reviewed agents through blocking the OATP transporters (nontoxic nostocyclopeptide-M1, captopril, and naringin), then inhibition of MC-LR uptake (naringin, rifampin, cyclosporin-A, silymarin and captopril), and finally at restoration of PPAse activity (silybin, quercetin, morin, naringin, rifampin, captopril, azo dyes) exert hepatoprotective effect against MC-LR.

Hepatoprotective effect of amifostine and WR-1065 on acetaminophen-induced liver toxicity on Wistar rats.

PURPOSE: The most important problem with acetaminophen is its hepatotoxicity. N-acetylcysteine (NAC) is used to treat the hepatotoxicity of acetaminophen. Due to the structural similarities of this compound with amifostine, we decided to test the effect of this substance and its metabolite, WR-1065, on the hepatotoxicity of acetaminophen. METHODS: The single-dose method contained 1. Control; 2. Acetaminophen (1 g/kg, gavage); 3-5. Acetaminophen + amifostine (100, 200, 400 mg/kg, i.p.); 6-8. Acetaminophen + WR-1065 (50, 100, 200 mg/kg, i.p.); and 9. Acetaminophen + NAC (100, 200 mg/kg, i.p.). The multiple-dose method included the same groups: amifostine (50, 100, 200 mg/kg), WR-1065 (25, 50, 100 mg/kg), and NAC (100 mg/kg). Then, animals were sacrificed, and blood samples were collected for measuring ALT, AST, ALP, and T-Bil, liver tissue for histopathological examination, MDA, and GSH amounts. RESULTS: Acetaminophen increased the levels of MDA, T-Bil, ALT, AST, and ALP, decreased GSH levels, and augmented necrosis, neutrophils, lymphocytes, and macrophages in the port space in single-dose and multiple-dose studies. Amifostine and WR-1065 significantly reduced the levels of MDA, T-Bil, ALT, AST, ALP, increased GSH content, and ameliorated histopathological alterations in a single-dose and multiple-dose method compared to the acetaminophen group. Moreover, NAC caused a significant decrease in the levels of MDA, T-Bil, ALT, AST, and ALP, and reduced GSH amounts in single-dose and multiple-dose studies. CONCLUSION: Amifostine and WR-1065 as antioxidant and hepatoprotective compounds are effective in reducing acetaminophen-induced hepatotoxicity with a similar effect to NAC and can be administered as an adjunct in the treatment of acetaminophen overdose.

Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs.

This Medical News article discusses a recent study that examined the remedies most often recommended on Reddit for diluting psychedelic experiences.

Gastroprotective effects of Chinese Rana chensinensis skin collagen against ethanol-induced gastric ulcer in mice.

Gastric ulcer is a common gastrointestinal disease caused by excessive gastric acid secretion, which has been recognized as one of the most common causes of morbidity and mortality in the world. The skin of Rana chensinensis is rich in collagen and many previous studies have shown that it has certain bioactivity. Therefore, we extracted and purified collagen with a molecular weight less than 10000 Da from the skin of Rana chensinensis, and studied its gastric protective mechanism through the model of ethanol-induced gastric ulcer in Balb/c mice. The results showed that through macroscopic observation and significantly reduced ulcer index, it was proved that PCRCS could protect gastric mucosa and alleviate the damage of ethanol to gastric mucosa. PCRCS reduced ethanol-induced oxidative stress by boosting depleted SOD levels and dramatically lowering MDA levels, as well as significantly reducing lipid peroxidation. Additionally PCRCS (Protein Chinese Rana chesinensis Skin) additionally decreased the launch of inflammatory mediators TNF-α and IL-6 and more desirable the content material of protective elements NO and PGE2 in gastric mucosa. Based on these findings, we believe that PCRCS has potential stomach protective effects on ethanol-induced gastric ulcer, which may be achieved by inhibiting oxidative stress and stomach inflammation.

The prescribing of cardioprotective medications and the impact on survival for patients with peripheral artery disease that undergo intervention.

BACKGROUND: Cardiovascular disease guidelines recommend that patients with established peripheral artery disease (PAD) are prescribed antihypertensive, lipid-lowering, and antiplatelet medication to reduce cardiovascular ischaemic events. However, the prescribing of these medications for patients with PAD within New Zealand (NZ) remains undefined. METHODS: This was a retrospective observational cohort study of patients in the Midland region of NZ, that underwent PAD-related percutaneous and surgical intervention between 1st January 2010 and 31st December 2021. Patient level data was collected. The primary outcome was prescribing of cardioprotective medications either before or within 1 year of incident procedure. Secondary outcome was overall survival. RESULTS: There were 2547 patients included. Antihypertensive prescription occurred in 80.7%, lipid-lowering in 77.4% and antithrombotic in 89.9%. Concomitant ischaemic heart disease increased prescription of cardioprotective medications. Women were prescribed less lipid-lowering medication compared to men. Maori men were prescribed less antiplatelet medication compared to non-Maori men. On univariate analysis lipid-lowering and antiplatelet medication showed survival advantage, while antihypertensive and anticoagulation did not. After adjustment for age, sex, end stage renal failure and presence of chronic limb-threatening ischaemia, best medical therapy was associated with better survival (HR 0.88, 95% CI 0.79-0.98, P = 0.02). CONCLUSION: This study highlights areas of deficiency in prescribing of cardioprotective medication in this high-risk group. These could be targets for national quality improvement initiatives.

Cisplatin-induced ototoxicity: a novel approach to an ancient problem.

With the scarcity of pharmacological otoprotective agents against cisplatin-induced ototoxicity (CIO), researchers find themselves compelled to look at and navigate all possible strategies to identify ways to prevent CIO. One of these promising strategies is pharmacogenomic implementation. This strategy aims for identifying and detecting high-risk genetic variants to tailor cisplatin therapy to reach the best survival outcomes with the least risk of ototoxicity.

Is the combination of linagliptin and allopurinol better prophylaxis against post-contrast acute kidney injury? A multicenter prospective randomized controlled study.

BACKGROUND: Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD. METHODS: Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2nd received allopurinol, the 3rd group received linagliptin, and the 4th received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients. RESULTS: 20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 (p < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis. CONCLUSION: Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03470454.

Metabolic heterogeneity caused by HLA-DRB1*04:05 and protective effect of inosine on autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an autoimmune disease caused by disruption of liver immune homeostasis. Genetic studies have revealed the predisposition of AIH with the human leukocyte antigen (HLA) region. Recently, metabolomics integrated with genomics has identified many genetic loci of biomedical interest. However, there is no related report in AIH. In the present study, we found that HLA-DRB1*04:05 was linked to the clinical features and prognosis of AIH in Chinese patients. Furthermore, our patients were divided into DRB1*04:05 positive and DRB1*04:05 negative groups and the metabolic profiling was done by HPLC/MS. We chose inosine, one of the highly altered metabolites, to explore the effect on an acute severe hepatitis murine model. The results showed that inosine treatment attenuated hepatocyte apoptosis, enhanced antioxidant ability and inhibited the activation and glycolysis of CD4+ T cell. We propose that inosine participates in the regulation of AIH through its protective effect on hepatocytes and inhibition of overactivated immune cells, which might provide a potential novel approach in treating acute form of AIH.