Identification of Histopathological Biomarkers in Fatal Cases of Coronavirus Disease: A Study on Lung Tissue

We aimed to evaluate the primary lung postmortem macro- and microscopic biomarkers and factors associated with diffuse alveolar damage in patients with fatal coronavirus (COVID-19). We retrospectively analyzed lung tissue collected from autopsies performed in Cluj-Napoca, Romania, between April 2020 and April 2021 on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We examined 79 patients with confirmed SARS-CoV-2 infection, ages 34 to 96 years, split into two groups using the cut-off value of 70 years. Arterial hypertension (38%) and type 2 diabetes mellitus (19%) were the most common comorbidities with similar distribution between groups (p-values > 0.14). Macroscopically, bloody exudate was more frequently observed among patients p-value = 0.0091). Diffuse alveolar damage (53.1%) was similarly observed among the evaluated groups (p-value = 0.1354). Histopathological biomarkers of alveolar edema in 83.5% of patients, interstitial pneumonia in 74.7%, and microthrombi in 39.2% of cases were most frequently observed. Half of the evaluated lungs had an Ashcroft score of up to 2 and an alveolar air capacity of up to 12.5%. Bronchopneumonia (11/43 vs. 3/36, p-value = 0.0456) and interstitial edema (9/43 vs. 2/36, p-value = 0.0493) were significantly more frequent in older patients. Age (median: 67.5 vs. 77 years, p-value = 0.023) and infection with the beta variant of the virus (p-value = 0.0071) proved to be significant factors associated with diffuse alveolar damage

Effects of Curcumin Nanoparticles in Isoproterenol-Induced Myocardial Infarction

Curcumin has anti-inflammatory, antioxidative, anticarcinogenic, and cardiovascular protective effects. Our study is aimed at evaluating the effects of pretreatment with curcumin nanoparticles (CCNP) compared to conventional curcumin (CC) on isoproterenol (ISO) induced myocardial infarction (MI) in rats. Fifty-six Wistar-Bratislava white rats were randomly divided into eight groups of seven rats each. Curcumin and curcumin nanoparticles were given by gavage in three different doses (100 mg/kg body weight (bw), 150 mg/kg bw, and 200 mg/kg bw) for 15 days. The MI was induced on day 13 using 100 mg/kg bw ISO administered twice, with the second dose 24 h after the initial dose. The blood samples were taken 24 h after the last dose of ISO. The antioxidant, anti-inflammatory, and cardioprotective effects were evaluated in all groups. All doses of CC and CCNP offered a cardioprotective effect by preventing creatine kinase-MB leakage from cardiomyocytes, with the best result for CCNP. All the oxidative stress parameters were significantly improved after CCNP compared to CC pretreatment. CCNP was more efficient than CC in limiting the increase in inflammatory cytokine levels (such as TNF-α, IL-6, IL-1α, IL-1β, MCP-1, and RANTES) after MI. MMP-2 and MMP-9 levels decreased more after pretreatment with CCNP than with CC. CCNP better prevented myocardial necrosis and reduced interstitial edema and neutrophil infiltration than CC, on histopathological examination. Therefore, improving the bioactivity of curcumin by nanotechnology may help limit cardiac injury after myocardial infarction

Curcumin Nanoparticles Protect against Isoproterenol Induced Myocardial Infarction by Alleviating Myocardial Tissue Oxidative Stress, Electrocardiogram, and Biological Changes

Curcumin from Curcuma longa is a nutraceutical compound reported to possess strong antioxidant activity that makes it a candidate for use in counteracting oxidative stress-induced damage. The effect of pre-treatment with curcumin nanoparticles (nC) compared to conventional curcumin (Cs) on blood pressure, electrocardiogram, and biological changes on isoproterenol (ISO)-induced myocardial infarction (MI) in rats had been investigated. The Cs doses of 150 and 200 mg/kg bw and all nC doses (100, 150 and 200 mg/kg bw) significantly reduced heart rate before ISO administration and prevented QRS complex enlargement after MI induction (p < 0.026). All doses of Cs and nC prevented prolongation of the QT and QT corrected (QTc) intervals, with better results for higher doses (p < 0.048). The nC solution had more significant results than Cs in all metabolic parameters assessed (lactate dehydrogenase, glycaemia, aspartate transaminase, and alanine transaminase, p < 0.009). nC was more efficient than Cs in limiting myocardial oxidative stress and enhancing antioxidative capacity (p < 0.004). Compared to Cs, nC better prevented myocardial damage extension, reduced interstitial oedema, and inflammation. Curcumin nanoparticles as compared to conventional curcumin exert better antioxidative effects. Moreover, nC better prevent cardiomyocytes damage, and electrocardiogram alterations, in the case of ISO-induced MI in rats

Curcumin Nanoparticles Enhance Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation

We investigated the in vivo effect of curcumin nanoparticles (nC) in addition to diclofenac sodium on local edema and oxidative stress parameters in carrageenan-induced paw edema on rats. Seven groups were investigated: control group (C), the acute inflammation (AI) group, an AI group treated with Diclofenac (AID, 5 mg/kg b.w. Diclofenac sodium), two AI groups treated with cC (conventional Curcumin)—AIC200 and AIcC200D (D = Diclofenac, 200 represent the concentration of active substance expressed in mg/kg b.w.), and two AI groups with nC (Curcumin nanoparticles)—AIC200 and AIcC200D. Serum and tissue oxidative stress was assessed by measuring five parameters. Curcumin nanoparticles alone and in combination with D better reduced the paw edema than D alone (p < 0.027). The rats treated with D and nC (AIcC200D) had the highest inhibition percentage on edema, reaching the maximum level of inhibition (81%) after 24 h. Conventional curcumin and nC presented antioxidant effects in acute inflammation, with significantly better results obtained for nC. The pro-oxidant markers were reduced up to 0.3 by the cC and up to 0.4 times by the nC and both solutions increased the antioxidant markers up to 0.3 times. The nC enhanced the antioxidative efficacy of D, as this combination reduced the pro-oxidant markers up to 1.3 times. Curcumin nanoparticles could represent a therapeutic option in association with classical nonsteroidal anti-inflammatory medication in acute inflammation, as they might offer a reduction of drug dose and possible limitation of their associated side effects

Anti-Inflammatory and Analgesic Effects of Curcumin Nanoparticles Associated with Diclofenac Sodium in Experimental Acute Inflammation

The present study evaluated the anti-inflammatory and analgesic effects of conventional curcumin (cC) and curcumin nanoparticles (nC) associated with diclofenac sodium (D) in experimental acute inflammation (AI) induced by carrageenan administration. Seven groups of eight randomly selected Wistar-Bratislava white rats were evaluated. One group was the control (C), and AI was induced in the other six groups. The AI group was treated with saline solution, the AID group was treated with D, the AIcC200 and AInC200 groups were treated with cC and nC, respectively, while AIcC200D and AInC200D were treated with cC and nC, respectively, both associated with D. Conventional curcumin, nC, and D were administered in a single dose of 200 mg/kg b.w. for cC and nC and 5 mg/kg b.w. for D. Association of cC or nC to D resulted in significant antinociceptive activity, and improved mechanical pressure stimulation and heat thresholds at 3, 5, 7 and 24 h (p < 0.03). The association of cC and nC with D (AIcC200D and AInC200D groups) showed significantly lower plasma and tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) up to 2.5 times, with the best results in the group who received nC. Moreover, AInC200D presented the least severe histopathological changes with a reduced level of inflammation in the dermis and hypodermis. The combination of nC to D showed efficiency in reducing pain, inflammatory cytokines, and histological changes in acute inflammation

Multi-Organ Protective Effects of Curcumin Nanoparticles on Drug-Induced Acute Myocardial Infarction in Rats with Type 1 Diabetes Mellitus

The objectives of this study were to investigate the cardio-protective, hepatoprotective and nephroprotective effects of curcumin nanoparticle (NC) pretreatment compared to conventional curcumin (CC) on acute myocardial infarction (AMI) in rats with type 1 diabetes mellitus (T1DM). Fifty-six Wister Bratislava rats were divided into eight groups. The first four groups—C (control group), AMI (group with AMI), T1DM (group with T1DM), and T1DM-AMI (group with T1DM and AMI)—received only saline (S) during the whole experiment. Two groups—S-T1DM-CC-AMI and S-T1DM-NC-AMI—were pretreated with S before T1DM induction. The S-T1DM-CC-AMI group received CC (200 mg/Kg bw (bw—body weight)) after T1DM induction, while the S-T1DM-NC-AMI group received NC (200 mg/Kg bw) after T1DM induction. the CC-T1DM-CC-AMI group received CC (200 mg/Kg bw) during the whole experiment. Similarly, the NC-T1DM-NC-AMI group received NC (200 mg/Kg bw) over the entire experiment. T1DM was induced on day 7 using a single dose of streptozotocin (STZ). AMI was induced with isoproterenol (ISO) on day 22. Both curcumin formulations, CC and NC, prevented the following electrocardiographic changes: prolongation of the QRS complex, enlargement of QT and QTc intervals, and ST-segment elevation. Glucose levels and lipid profile parameters were reduced up to 1.9 times, while C-peptide serum levels were increased up to 1.6 times in groups that received CC or NC. Liver function parameters (aspartate transaminase, alanine transaminase) and kidney function parameters (creatinine, urea) were reduced 4.8 times, and histological changes of liver and kidney tissue were improved by CC or NC administration. Pretreatment with NC proved significantly higher cardioprotective, hepatoprotective and nephroprotective effects in the case of AMI in T1DM