3-Indolepropionic Acid Prevented Chlorpyrifos-Induced Hepatorenal Toxicities in Rats By Improving Anti-Inflammatory, Antioxidant And Apoptotic Responses and Abating DNA Damage

We examined the individual and combined effect of 3-Indolepropionic acid (IPA) and Chlorpyrifos (CPF) on rat hepatorenal function. The experimental cohorts (n=6) were treated per os for 14 consecutive days as follows: Control (Corn oil 2 mL/kg body weight), CPF alone (5 mg/kg), IPA alone (50 mg/kg) and the co-treated cohorts (CPF: 5 mg/kg + IPA: 25 or 50 mg/kg). Biomarkers of hepatorenal damage, antioxidant and myeloperoxidase (MPO) activities, the levels of nitric oxide (NO), lipid peroxidation (LPO) and reactive oxygen and nitrogen (RONS) species were spectrophotometrically evaluated. Besides, the concentration of tumour necrosis factor-alpha (TNF- α), interleukin-1 β (IL-1β) and caspase-3 activity and 8-hydroxy-2’-deoxyguanosine adducts (8-OHdG) was also assessed by Enzyme-Linked Immunosorbent Assay. Treatment with CPF alone increased biomarkers of hepatorenal toxicity was significantly (p<0.05) alleviated in rats co-exposed to CPF and IPA. Moreover, the decrease in antioxidant status as antioxidant elevation in RONS and LPO were lessened (p<0.05) in rats co-treated with CPF and IPA. CPF mediated increases in TNF-α, IL-1β, NO, MPO and caspase-3 activity were reduced (p<0.05) in the liver and kidney of rats co-exposed to CPF and IPA. In addition, 8-OHdG adducts formation were reduced in rats treated with 3-IPA dose-dependently. Light microscopic examination showed that histopathological lesions severity induced by CPF were alleviated in rats co-exposed to IPA and CPF. In conclusion, the results demonstrated that rats co-exposed to IPA and CPF exhibited reduced CPF-induced oxidative stress, inflammation, DNA damage and caspase-3 activation of the liver and kidney.

Prognostic value of longitudinal assessment of hepatorenal function and nutritional status in patients undergoing valvular heart surgery

Background Hepatorenal dysfunction and malnutrition are frequent extracardiac consequences of valvular heart disease (VHD) and have emerged as prominent drivers of adverse prognosis in selected valvular interventions. Nonetheless, data in a general VHD population is sparse, and their interaction and changes following valvular surgery remain unexplored. Purpose We aim to characterise the temporal changes, interaction, and prognostic implications of hepatorenal dysfunction and malnutrition before and after valvular surgery. Methods Baseline and temporal changes in hepatorenal dysfunction (assessed by the modified model for end-stage liver disease [MELD-XI] score) and nutritional status (assessed by Controlling Nutritional Status [CONUT] score) were correlated with adverse events (composite of all-cause mortality and hospitalisation for heart failure) using Cox proportional hazards model, adjusted with clinical and echocardiographic covariates, medications, type of valvular procedure, and cardiac surgery risk-stratification models (EuroSCORE II and STS score). Results Our study included 909 patients who underwent valvular surgery. At baseline, 216 (24%) and 554 (61%) had hepatorenal dysfunction (MELD-XI &gt;12.43) and malnutrition (CONUT ≥2), respectively. MELD-XI scores were modestly correlated with CONUT scores (R=0.36, p&lt;0.001), with concomitant hepatorenal dysfunction and malnutrition present in 177 (19%) patients. Over a median follow-up of 4.1 years, 101 (11%) patients died and 119 (13%) were hospitalised for heart failure. There was a stepwise increase in mortality (χ2 89.1, p&lt;0.001) and adverse events (χ2 92.9, p&lt;0.001) from patients with normal hepatorenal function and nutrition to concomitant hepatorenal dysfunction and malnutrition (Figure 1). This association remained consistent in fully adjusted models. MELD-XI and CONUT scores significantly improved the discriminatory accuracy of EuroSCORE II (area under the curve [AUC]: 0.80 vs 0.73, p&lt;0.001) and STS score (AUC: 0.79 vs 0.72, p=0.004) for all-cause mortality. In patients with MELD-XI and CONUT scores 1 year after surgery (n=707), ΔMELD-XI (follow-up MELD-XI minus baseline MELD-XI score) and ΔCONUT scores were significantly associated with adverse events (HR 1.08, 95% CI 1.03–1.14, p=0.001 for ΔMELD-XI; HR 1.18, 95% CI 1.02–1.35, p=0.02 for ΔCONUT). Patients remaining with hepatorenal dysfunction and malnutrition experienced worse survival (log-rank χ2 65.2, p&lt;0.001) and adverse events (log-rank χ2 90.4, p&lt;0.001) (Figure 2). Conclusions In patients undergoing valvular surgery, hepatorenal function and nutritional status at baseline, and their temporal changes, are strongly linked to clinical outcomes. These results highlight the role of hepatorenal and nutritional assessment for risk-stratification in valvular surgery. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Efficacy and Safety of Ningmitai Capsules in Patients with Chronic Epididymitis: A Prospective, Parallel Randomized Controlled Clinical Trial

Objectives. To evaluate the efficacy and safety of Ningmitai (NMT) capsules in patients with chronic epididymitis. Methods. This prospective randomized controlled trial included 112 patients diagnosed with chronic epididymitis. The patients were randomized (1 : 1 : 1) to receive levofloxacin (LVX), NMT, or NMT combined with LVX for 4 weeks. The patients were followed up at 2 and 4 weeks after initiation of treatment and were evaluated in terms of Chronic Epididymitis Symptom Index (CESI) scores, epididymal nodules, and safety parameters. The primary endpoints were the CESI scores at the end of 2 and 4 weeks of treatment. The secondary endpoints included the mean epididymal nodule diameter and the clinical efficacy rate. Safety was evaluated by hepatorenal function tests and adverse event reports during the trial. Results. After 2 weeks of treatment, the CESI score of the NMT group was significantly lower than that of the LVX group ( P < 0.05 ). In addition, the clinical efficacy rate of the NMT group was significantly higher than that of the LVX group (55% vs. 8.33%, P < 0.0001 ), indicating that NMT has a rapid effect on chronic epididymitis. After 4 weeks of treatment, there was no significant difference in CESI scores or clinical efficacy rates between the two monotherapy regimens ( P > 0.05 ); however, the mean diameter of epididymal nodules was significantly smaller in the NMT group than in the LVX group ( P < 0.0001 ). Moreover, after 4 weeks of treatment, the patients in the LVX + NMT group, which had a clinical efficacy rate of 97.22%, had lower CESI scores (both P < 0.01 ) and a smaller epididymal nodule diameter (vs. LVX, P < 0.0001 ; vs. NMT, P < 0.05 ) than those in the other two groups. No adverse events or abnormal hepatorenal function were found during the study. Conclusion. NMT significantly improved CESI scores and epididymal nodule diameter in patients with chronic epididymitis. The combination of NMT and LVX provides a much better effect than monotherapy, and this treatment regimen was well tolerated.

A Novel Sirolimus-eluting Biodegradable Magnesium-based Alloy Scaffold: Six-month Results In Porcine Peripheral Arteries

Purpose: Magnesium-based alloy scaffold is a promising biodegradable stent due to its intrinsic mechanical performance and biocompatibility. Based on our preliminary experiments, we designed a novel sirolimus-eluting magnesium-based alloy scaffold. This work aimed to assess its safety and degradation performance in vivo. Methods: The scaffolds were implanted in the lower limb arteries of Bama mini-pigs. Safety was defined as no immediate thrombosis or >30% residual stenosis, which was assessed with optical coherence tomography and digital subtraction angiography. Blood biochemical analyses were performed to evaluate hepatorenal toxicity. The degradation process of the scaffolds, the endothelialization, and lumen loss of the stented-vessels were detected with scanning electron microscopy, immunohistochemical, hematoxylin-eosin staining and optical coherence tomography. Results: Twenty-four scaffolds were successfully implanted in six pigs with no signs of immediate thrombosis or >30% residual stenosis. The scaffolds were covered by endothelium at one month and absolutely resorbed at six months post implantation. Blood analysis showed that the hepatorenal function except for alanine aminotransferase and γ-glutamyl transpeptidase was normal. Obvious intimal hyperplasia and lumen loss were found in the stented vessels at three months, while the diameters and inner lumen areas of stented segments had increased significantly at six months (p

Chlorogenic acid abates oxido-inflammatory and apoptotic responses in the liver and kidney of Tamoxifen-treated rats

Plant-derived phenolics are utilized as chemopreventive agents to abate adverse toxic responses associated with drug-induced damages. Tamoxifen (TAM)—a chemotherapeutic agent—is used in managing all stages of hormone-dependent breast cancer. Notwithstanding TAM’s clinical side effect—including hepatic toxicity—its use is commonplace. The present study investigates the effect of Chlorogenic acid (CGA: 25 and 50 mg kg−1; per os (p.o)) reported to exhibit various beneficial properties, including antioxidative effect against TAM (50 mg/kg; p.o.)-induced hepatorenal toxicities in rats treated as follows: Control, CGA, or TAM alone, and rats co-treated with CGA and TAM for 2 weeks. Biomarkers of hepatorenal function, oxido-inflammatory stress, and hepatorenal histopathology were performed. We observed that TAM alone decreased relative organ weights (ROW), marginally impacted rat’s survivability, and significantly (P &lt; 0.05) increased hepatorenal toxicities and reactive oxygen and nitrogen species (RONS). TAM decreased (P &lt; 0.05) antioxidant, anti-inflammatory cytokine (IL-10), besides increase in (P &lt; 0.05) lipid peroxidation (LPO), pro-inflammatory cytokines (IL-1β, TNF-α), nitric oxide (NO), xanthine oxidase (XO), myeloperoxidase (MPO), and apoptotic caspases (Casp-3 and -9) levels. These biochemical alterations were accompanied by morphological lesions in experimental rats’ liver and kidney. Conversely, that CGA dose-dependently relieved TAM-mediated toxic responses, restored antioxidants capacities, reduced oxidative stress, pro-inflammatory cytokines levels, and Casp-3 and -9 activities in experimental rats. Furthermore, CGA protected against lesions observed in the liver and kidney of rats treated with TAM alone. Overall, CGA blocked TAM-mediated hepatorenal injuries associated with pro-oxidative, inflammatory, and apoptotic mechanisms. CGA may serve as a chemoprotective agent boosting patients prognosis undergoing TAM chemotherapy.

Ethanol leaf extract of Jatropha tanjorensis ameliorates hepatorenal toxicity of Plasmodium berghi-berghi infected mice treated with Hippocratea africana root bark extract

The effect of ethanol leaf extract of Jatropha tanjorensis on hepatorenal function of Plasmodium berghiberghi infected mice treated with root bark extract of Hippocratea africana was evaluated. Twenty-One (21) male mice weighing between 27 – 33 g used for the study were divided into seven groups. Group 1 served as normal control while Groups 2 – 7 were parasitized with Plasmodium berghi-berghi and Group 2 was the test control group (parasitized without treatment). Group 3 was administered 8 mg/kg bw of artemether-lumefantrine for 3 days. Group 4 and 5 received daily, 200 mg/kg bw and 300 mg/kg bw of Hippocratea africana and Jatropha tanjorensis respectively for 4 days. Group 6 received 8mg/kg bw of artemether-lumefantrine for 3 days followed with 300 mg/kg bw of Jatropha tanjorensis for 4 days. Group 7 was treated with 200 mg/kg bw of Hippocratea africana for 4 days followed by 300 mg/kg bw of Jatropha tanjorensis for 4 days. The concentration of urea, creatinine and the activities of the liver enzymes were observed to increase significantly following induction of malaria when compared to normal control. Treatment with artemether-lumefantrine and root bark extract of Hippocratea africana showed drug induced hepatorenal toxicity which was ameliorated with the administration of ethanol leaf extract of Jatropha tanjorensis. The study showed that Jatropha tanjorensis leaf extract had hepatorenal protective function against Plasmodium berghi-berghi infection and malaria treatment induced toxicity, that may be due to its rich phytochemicals with antioxidant activity.

Lymphocytopenia and neutrophilia deteriorate at the lowest oxygenation index timepoint in COVID-19 patient

BackgroundCoronavirus disease 2019 (COVID-19) spread throughout the world and caused hundreds of thousands of infected people to death. However, the pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS COV-2) is poorly understood. The objective of this study is to retrospectively explore the pathogenesis of COVID-19 from clinical laboratory findings, taking disease progression into account.MethodsA single-centered, retrospective study was carried out, which included moderate (n=76) and severe COVID-19 cases (n=22). The difference of laboratory findings from blood routine examination and hepatorenal function test were retrospectively evaluated between the state of moderate and severe. The disease progression was indicated by oxygenation index.ResultsAge is a risk factor for disease progression from moderate to severe. Lymphocytopenia, neutrophilia, liver and kidney function decreasement occurred in severe patients on admission, compared with moderate patients. Lymphocytopenia and neutrophilia deteriorated at the lowest oxygenation index timepoint in the severe patients. And the oxygenation index was associated with ratio of lymphocyte and neutrophil in COVID-19 patients.ConclusionsLymphocytopenia and neutrophilia, which deteriorate in the progression of severe patients, are the main pathogenesis of COVID-19. More measures need to be taken to control lymphocytopenia and neutrophilia in severe COVID-19. Oxygenation index presented potentiality as predictor on the progression of COVID-19.