Potential benefits of using hydrogen sulfide, vitamin E and necrostatin-1 to counteract acetaminophen­induced hepatotoxicity in rats.

BACKGROUND: The use of acetaminophen (APAP) is increasing recently, especially with COVID-19 outbreaks. APAP is safe at therapeutic levels, however, an overdose can cause severe liver injury. This study aims to explore possible mechanisms involved in APAP­induced hepatotoxicity and compare different hepatoprotective agents, namely vitamin E, hydrogen sulfide (H2S) and necrostatin-1 (NEC-1). METHODS: Adult male albino rats were divided into groups: Control group, APAP­induced hepatotoxicity group, Vitamin E­treated group, H2S­treated group and NEC-1­treated group. Serum levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-33 (IL-33), tumor necrosis factor alpha (TNF-α), reduced glutathione (GSH) and lipid profile were measured. Histopathological examinations of liver tissue with H(et)E stain and immunohistochemistry for activated caspase-3 were also done. RESULTS: APAP­treated group showed elevated liver transaminases, hyperlipidemia, and deficient liver anti-oxidative response together with disturbed hepatic architecture and increased immune-expression of activated caspase-3 in hepatic tissue. Pretreatment with vitamin E, H2S or NEC-1 reversed the affected parameters. Vitamin E and H2S showed greater improvement when compared to NEC-1. CONCLUSION: Vitamin E, H2S and NEC-1 showed protective effects against APAP-induced hepatotoxicity, thus they may be used as an adjuvant therapy when APAP is indicated for long periods as is the case in COVID-19 patients (Tab. 2, Fig. 2, Ref. 45). Text in PDF www.elis.sk Keywords: acetaminophen, hepatotoxicity, apoptosis, necrostatin-1, vitamin E, H2S.

Effect of a newly synthesized quinoline-based compound (PPQ-8) on murine schistosomiasis mansoni.

Schistosomiasis represents a public health problem and praziquantel is the only drug used for treatment of all forms of the disease. Thus, the development of new anti-schistosomal agents is of utmost importance to increase the effectiveness, reduce side effects and delay the emergence of resistance. The present study was conducted to report the therapeutic efficacy of PPQ-8, a new synthetic quinoline-based compound against Schistosoma mansoni. Mice were treated with PPQ-8 at day 49 post infection using two treatment regimens (20 and 40 mg/kg). Significant reductions were recorded in hepatic (62.9% and 83.6%) and intestinal tissue egg load (57.4% and 73.5%), granuloma count (75.4% and 89.1%) and diameter (26.2% and 47.3%), in response to the drug regimens, respectively. In addition, both treatment regimens induced significant decrease in liver (23.3% and 32.8%) and spleen (37.5% and 45.3%) indices. Also, there were significant reductions in mature ova, total worm and female count, which were more prominent with the higher dose. The reduction in the level of nitric oxide in the liver by both therapeutic regimens to 22.5% and 47.2% indicates the anti-oxidant activity of PPQ-8. Bright field microscopic examination of worms recovered from infected and PPQ-8-treated mice showed nearly empty intestinal caeca with no observable changes in the tegument. Our findings hold promise for the development of a novel anti-schistosomal drug using PPQ-8, but further in vitro and in vivo studies are needed to elucidate the possible mechanism/s of action and to study the effect of PPQ-8 on other human schistosomes.

Effect of different surface treatments and ceramic primers on shear bond strength of self-adhesive resin cement to zirconia ceramic.

AIMS: To evaluate the effect of different surface treatments and ceramic primers on the shear bond strength (SBS) of self-adhesive resin cement to zirconia ceramic. MATERIALS AND METHODS: A total of 40 zirconia discs (10 mm in diameter and 3 mm in height; StarCeram Z-Med, H.C. Starck, Selb, Germany) were prepared from pre-sintered zirconia blocks. Discs were divided into two groups according to surface treatment: (a) airborne particle abrasion (sandblasting) with 50-µm Al2O3 particles and (b) 9.5% hydrofluoric acid etching. Each of these groups was subdivided into two groups according to the type of primer applied: (a) Z-Prime Plus primer and (b) Clearfil Ceramic Primer. A self-adhesive resin cement (Multilink Speed, Ivoclar Vivadent, Schaan, Liechtenstein) was used to bond with polyethylene molds. All specimens were tested at thermocycled (5000 cycles at 5-55°C for 30 s) conditions. The SBS of the luting cement to the ceramic was measured in a universal testing machine (1 mm/min). RESULTS: The sandblasted groups showed significantly higher SBS values than the acid-etched groups for both primers (P = 0.0001). Independent of the surface treatment, the Z-Prime Plus primer groups showed higher SBS values than the Clearfil Ceramic Primer groups (P = 0.0001). CONCLUSIONS: Sandblasting is a more effective method to increase bond strength on zirconia ceramics than hydrofluoric acid etching, and the application of Z-Prime Plus primer increases SBS better than Clearfil Ceramic Primer.