Aquatic ecosystem health is the main concern to increasing pesticides application to control agricultural pests as it is the ultimate receptor of such materials. This study evaluated the impact of new metal-insecticide, the [Mg(hesp)₂(phen)], referred as MgHP, on fish using physiological, genetic, biochemical, and morphological biomarkers. The fish, Prochilodus lineatus, was exposed to 0 (control), 1, 10, 100, 1000 μg L⁻¹ MgHP, for 24 and 96 h. MgHP was not lethal but caused genotoxicity, altered hematological variables and, the activity of antioxidant and biotransformation enzymes and histology of liver, depending on concentration and time exposure. Hematocrit and erythrocyte number (RBC) increased without change hemoglobin content resulting in changes in hematimetric indexes after 24 h; after 96 h, only RBC was changed. Erythrocyte nuclear abnormalities and crenate cells increased after 24 h but, not after 96 h. Erythrocytes and hepatocytes indicated instability in DNA integrity however, the absence of micronuclei suggested DNA damage repairment. After 24 h, the antioxidant defense system and the phase II biotransformation enzyme was responsiveness and catalase activity decreased at high MgHP concentrations; the antioxidant response was triggered after 96 h. Hepatocyte hypertrophy, intracellular cytoplasmic substances, cytoplasm degeneration, melanomacrophage and hyperemia increased in fish exposed from 10 μg L⁻¹ to higher MgHP concentrations; the organ alteration index increased as MgHP concentration increased showing dose-dependence. Most of hematological and genotoxic effects occurred after 24 h exposure evidencing potential recover capability of organism by activation of the antioxidant defense system and DNA repairment mechanisms. Nevertheless, the histopathological changes in the liver was maintained over time at high MgHP concentrations, a concentration usually no environmental relevant. In conclusion, this data reinforced the importance of continuing research on MgHP effects in other organisms considering the promising use of such compound to control the leaf-cutter ants and other insects.

Arsenic (As) toxicity is a problem that needs to be solved in terms of both human health and agricultural production in the vast majority of the world. The presence of As causes biomass loss by disrupting the balance of biochemical processes in plants and preventing growth/water absorption in the roots and accumulating in the edible parts of the plant and entering the food chain. A critical method of combating As toxicity is the use of biosafe, natural, bioactive compounds such as hesperidin (HP) or chlorogenic acid (CA). To this end, in this study, the physiological and biochemical effects of HP (100 μM) and CA (50 μM) were investigated in Zea mays under arsenate stress (100 μM). Relative water content, osmotic potential, photosynthesis-related parameters were suppressed under stress. It was determined that stress decreased the activities of the antioxidant system and increased the level of saturated fatty acids and, gene expression of PHT transporters involved in the uptake and translocation of arsenate. After being exposed to stress, HP and CA improved the capacity of superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), glutathione S-transferase (GST) and glutathione peroxidase (GPX) and then ROS accumulation (H₂O₂) and lipid peroxidation (TBARS) were effectively removed. These phenolic compounds contributed to maintaining the cellular redox status by regulating enzyme/non-enzyme activity/contents involved in the AsA-GSH cycle. HP and CA reversed the adverse effects of excessive metal ion accumulation by re-regulated expression of the PHT1.1 and PHT1.3 genes in response to stress. Exogenously applied HP and CA effectively maintained membrane integrity by regulating saturated/unsaturated fatty acid content. However, the combined application of HP and CA did not show a synergistic protective activity against As stress and had a negative effect on the antioxidant capacity of maize leaves. As a result, HP and CA have great potentials to provide tolerance to maize under As stress by reducing oxidative injury and preserving the biochemical reactions of photosynthesis.

Nephrotoxicity is a very important complication of 5-fluorouracil (5-FU)–treated cancer patients. Increased oxidative stress, kidney damage, and apoptosis play an important role in the pathogenesis of nephrotoxicity caused by 5-FU. In this study, protective effects of two natural compounds, hesperidin and curcumin, on experimentally induced kidney damage in mice with 5-FU were determined. Application of 5-FU resulted in severe histopathological changes and severe renal failure with increased serum urea and creatinine levels. Also, 5-FU–induced kidney damage, increased levels of malondialdehyde (MDA), decreased superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) activity, and glutathione (GSH) level have been demonstrated. Also, where 5-FU is in the concentration of caspase-3 and 8-OHdG immune-positive cells and therefore causes apoptosis and DNA damage in kidney tissue cells. However, especially high doses of hesperidin and curcumin treatment significantly improved 5-FU–induced oxidative stress/lipid peroxidation, apoptosis/DNA damage, and renal dysfunction. Based on these data, our results suggest that hesperidin and curcumin may be used as new and promising agents against 5-FU–induced nephrotoxicity.

It is known that some Campanula species are traditionally used because of their anti-allergic, spasmolytic, antiphlogistic, antioxidant, and antiviral properties. This study was designed to evaluate the phytochemical composition, antioxidant, α-amylase, and tyrosinase inhibitory activity of ethyl acetate, methanol, and water extracts of Campanula macrostachya Waldst. & Kit. ex Willd. Chemical compositions were analyzed by spectrophotometric and chromatographic methods. Antioxidant activities of the samples were tested by using five different test systems. Enzyme inhibitory activities of the extracts were also studied. As a result of the LC–ESI–MS/MS analyses, chlorogenic acid, hesperidin, and hyperoside were found to be the major compounds of the extracts, especially the MeOH extract (6559.59, 2499.22, and 2047.66 μg/g extract, respectively). Antioxidant activity tests have proven that MeOH extract showed higher activity than others (DPPH: 4.15 mg/mL, ABTS: 2.05 mg/mL, CUPRAC: 1.80 mg/mL, FRAP: 0.83 mg/mL, phosphomolybdenum: 1.69 mg/mL). Ferrous ion chelating activity of the water extract was 1.03 mg/mL. In α-amylase and tyrosinase inhibitory assays, EtOAc (IC₅₀: 2.54 mg/mL) and MeOH (IC₅₀: 1.51 mg/mL) extracts showed higher activity than the others did. In phosphomolybdenum, CUPRAC, FRAP, and tyrosinase inhibitory assays, the activity was strongly correlated with flavonoids, chlorogenic acid, hesperidin, and hyperoside. On the other hand, phenolic compounds have been found to contribute more to radical scavenging activity. Pearson correlation analysis showed that phenolics and flavonoids were not responsible for the α-amylase inhibitory activity of EtOAc extract.

Cardiovascular diseases are key complications primarily associated with hyperthyroidism disorders. The present study sought to ameliorate hyperthyroidism-mediated cardiovascular inflammations and related oxidative stress paradigms in experimental rats using the broadly distributed green seaweed Ulva fasciata. Forty-eight adult male albino rats were recruited and randomly classified into six groups. Hyperthyroidism was stimulated using L-thyroxine sodium at a dose of 100 μg/kg i.p. for 3 weeks daily. Further, 200 mg/kg b.wt. concentration of the U. fasciata methanolic (U. fasciata-MeOH) extract was the recommended dose and administrated orally to the hyperthyroid rats. The standard commercial drug “propranolol hydrochloride” was also tested at a dose of 10 mg/kg i.p. to compare the findings obtained from the seaweed extract. A combined treatment with the U. fasciata-MeOH extract and propranolol hydrochloride was also assessed. Our results implied that the treatment of hyperthyroid rats with the U. fasciata-MeOH extract significantly reduced serum levels of the thyroid hormones T3 and T4, proinflammatory cytokines (TNF-α, MPO, and CRP), triglycerides and total cholesterol, as well as the cardiac biomarkers CK-MB, LDH, and troponin to thresholds close to those of the standard drug. In addition, levels of high-density lipoprotein cholesterol (HDL-C) and interleukin 10 (IL-10) were significantly upregulated. Hyperthyroid rats only treated with propranolol hydrochloride, or with a combination of the drug and the seaweed extract, conferred the same observations. Histopathological architecture boosted our interesting findings where the myocardium tissues in hyperthyroid rats, administrated the U. fasciata-MeOH extract or/and propranolol hydrochloride, exhibited more or less a normal structure as the control, reflecting the potential cardiovascular recovery exerted by this seaweed extract. In vitro DPPH, ABTS, and FRAP antioxidant assays of the U. fasciata-MeOH extract showed an outstanding ROS-scavenging potential. HPLC analysis of the U. fasciata-MeOH extract unraveled an inestimable valuable array of phenolics (mainly p-coumaric, gallic, ferulic, chlorogenic, and syringic acids) and flavonoids (hesperidin, kaempferol, catechin, quercetin, and rutin). Conclusively, the seaweed U. fasciata is a profitable source of antioxidant polyphenolics characterized by having a pharmaceutical potential against hyperthyroidism-linked cardiovascular inflammations and oxidative stress patterns due to their substantial free radical quenching properties, and also via regulating the signalling pathways of the proinflammatory, lipid profile, and cardiac biomarkers.

In the scope of the study, the protective effect of hesperidin (HES), a flavanone glycoside, was investigated against sodium arsenite (NaAsO₂, SA) induced heart and brain toxicity. For this purpose, 35 Sprague-Dawley male rats were divided into 5 different groups, 7 in each group. Physiological saline was given to the first group. Dose of 200 mg/kg of HES to the second group, 10 mg/kg dose of SA to the 3rd group, 100 mg/kg HES and 10 mg/kg SA to the 4th group, 200 mg/kg HES, and 10 mg/kg SA to the 5th group were given orally for 15 days. At the end of the study, biochemical, histopathological, and immunohistochemical examinations were performed on the heart and brain tissues of the rats. According to the results, SA increased malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels and decreased glutathione (reduced, GSH) level and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in both tissues. Also, it increased cardiac lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CK-MB) activities and cardiac troponin-I level (cTn-I), cerebral acetylcholine esterase activity, nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1β), and cysteine aspartate-specific protease-3 (caspase-3) levels. In addition, as a result of histopathological examination, it was determined that SA damaged tissue architecture, and as a result of immunohistochemical examination, it increased cardiac Bcl-2-associated X protein (Bax) and cerebral glial fibrillary acidic protein (GFAP) expression. The results have also shown that HES co-treatment has an antioxidant, anti-inflammatory, antiapoptotic effect on SA-induced toxicity and aids to protect tissue architecture by showing a regulatory effect on all values. Consequently, it was determined that HES co-treatment had a protective effect on SA-induced heart and brain toxicity in rats.