Gastric ulceration is a common gastrointestinal ailment with serious consequences that can lead to serious illness or even death. This study aimed to examine the efficacy of tadalafil (TAD) and dexlansoprazole (DLP) in treating stomach ulcers caused by dexamethasone (DEX) in male albino Wister rats. Thirty male albino Wister rats were divided into 5 groups (6 rats each): control group received normal saline, positive control group received DEX 5 mg/kg/day intraperitoneal (i.p.) for 7 days, the third group received DLP 30 mg/kg/day orally after DEX, the fourth group received TAD 5 mg/kg/day orally after DEX, and the fifth group received DLP and TAD orally after DEX. Persistence and prevention of ulcers, pepsin activity, mucin content, and histopathological changes were evaluated after each trial. Reduced glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) levels were measured in gastric homogenates. Serum levels of prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) were also measured.  Treatment with either TAD or DLP alone significantly reduced ulcer index (U.I.), pepsin activity, TNF-α, IL-10 and MDA with significant rise in mucin content, PGE₂, NO, GSH, and improved the histological alteration compared to DEX group. When TAD and DLP were administered together, there was a more notable decrease in U.I., pepsin activity, gastric MDA, TNF-α, and IL-10 with concomitant more significant increase in mucin content, NO content, and PGE₂ production compared to the TAD or DLP groups alone. Compared to each medicine alone, TAD and DLP together have promising therapeutic potential in preventing stomach ulcers caused by DEX.

Abstract

Background

Acute liver failure (ALF) is a critical condition characterized by rapid liver dysfunction, leading to high mortality rates. Current treatments are limited, primarily supportive, and often require liver transplantation. This study investigates the potential of a novel nanoparticle formulation of glutathione (GSH) and virgin coconut oil (VCO) alone and in combination to enhance therapeutic outcomes in a rat model of ALF induced by orogastric carbon tetrachloride (CCl₄).

Methods

The study employed adult male Albino rats divided into ten groups, with ALF induced via a single oral dose of CCl₄. Various treatment regimens were administered over seven days, including conventional and nanoparticle forms of GSH and VCO and their combinations. The efficacy of treatments was evaluated through biochemical analysis of liver function markers, oxidative stress indicators, inflammatory biomarkers, and histopathological examinations. Nanoparticles were synthesized using established methods, and characterization techniques were employed to ensure their quality and properties.

Results

The nanoparticle formulations significantly improved liver function, as indicated by reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alongside decreased oxidative stress markers such as malondialdehyde. Furthermore, they reduced tumor necrosis factor alpha and interleukin-1 beta inflammatory markers. Histological analysis revealed reduced hepatocellular necrosis and inflammation in treated groups compared to controls. Also, decreased nuclear factor-kappa B was detected by immunohistochemical analysis.

Conclusion

The findings show that the nanoparticle mixture of GSH and VCO effectively reduces liver damage in ALF. This suggests a promising drug-based approach for improving liver regeneration and protection. This innovative strategy may pave the way for new therapeutic interventions in the management of ALF.

Abstract

In acute renal failure (ARF), the glomerular filtration rate is reduced, and nitrogenous waste products accumulate persistently, which can last anywhere from a few hours to several days. There is hope for a reversal of the rapid loss of renal function caused by this condition. This study, with gentamicin-induced acute ARF as a prospective setting, sets out to examine the reno-protective benefits of virgin coconut oil (VCO) and GSH. Furthermore, the study evaluated the effect of medication nanoparticle compositions on several kidney function markers. The induction of ARF is achieved with the intraperitoneal injection of gentamicin. To assess renal function, rats underwent 24 h of dehydration and hunger before their deaths. The study examined various aspects, including kidney function tests, markers of oxidative stress, histology of kidney tissue, inflammatory cytokines, immunohistochemistry expression of nuclear factor-kappa B (NF-κB), and specific biomarkers for kidney tissue damage, such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase–associated lipocalin (NGAL). The results of our study indicated that the combination of VCO and GSH, using both regular and nanoparticle formulations, had a better protective impact on the kidneys compared to using either drug alone. The recovery of renal tissue and serum markers, which are symptomatic of organ damage, indicates improvement. This was also demonstrated by the reduction in tubular expression of TNF-α, IL-1β, KIM-1, and NGAL. The immunohistochemical studies showed that the combination therapy, especially with the nanoforms, greatly improved the damaged cellular changes in the kidneys, as shown by higher levels of NF-κB. The study shows that VCO and GSH, when administered individually or combined, significantly improve ARF in a gentamicin-induced rat model, highlighting potential therapeutic implications. Notably, the combined nanoparticulate formulations exhibit substantial effectiveness.

Abstract

Purpose

Urolithiasis, the formation of kidney stones, is a common and severe condition. Despite advances in understanding its pathophysiology, affordable treatment options are needed worldwide. Hence, the interest is in herbal medicines as alternative or supplementary therapy for urinary stone disease. This review explores the use of plant extracts and phytochemicals in preventing and treating urolithiasis.

Methods

Following PRISMA standards, we systematically reviewed the literature on PubMed/Medline, focusing on herbal items evaluated in in vivo models, in vitro studies, and clinical trials related to nephrolithiasis/urolithiasis. We searched English language publications from January 2021 to December 2023. Studies assessing plant extracts and phytochemicals’ therapeutic potential in urolithiasis were included. Data extracted included study design, stone type, plant type, part of plant used, solvent type, main findings, and study references.

Results

A total of 64 studies were included. Most studies used ethylene glycol to induce hyperoxaluria and nephrolithiasis in rat models. Various extraction methods were used to extract bioactive compounds from different plant parts. Several plants and phytochemicals, including Alhagi maurorum, Aerva lanata, Dolichos biflorus, Cucumis melo, and quercetin, demonstrated potential effectiveness in reducing stone formation, size, and number.

Conclusions

Natural substances offer an alternative or supplementary approach to current treatments, potentially reducing pain and improving the quality of life for urolithiasis patients. However, further research is needed to clarify their mechanisms of action and optimize their therapeutic use. The potential of plant-based therapies in treating urolithiasis is promising, and ongoing research is expected to lead to treatment advancements benefiting patients globally.

Abstract

Since its identification in the vitreous humour of the eye and laboratory biosynthesis, hyaluronic acid (HA) has been a vital component in several pharmaceutical, nutritional, medicinal, and cosmetic uses. However, little is known about its potential toxicological impacts on aquatic inhabitants. Herein, we investigated the hematological response of Clarias gariepinus to nominal doses of HA. To achieve this objective, 72 adult fish were randomly and evenly distributed into four groups: control, low-dose (0.5 mg/l HA), medium-dose (10 mg/l HA), and high-dose (100 mg/l HA) groups for two weeks each during both the exposure and recovery periods. The findings confirmed presence of anemia, neutrophilia, leucopoenia, lymphopenia, and eosinophilia at the end of exposure to HA. In addition, poikilocytosis and a variety of cytomorphological disturbances were observed. Dose-dependent histological alterations in spleen morphology were observed in the exposed groups. After HA removal from the aquarium for 2 weeks, the groups exposed to the two highest doses still exhibited a notable decline in red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin concentration, and an increase in mean corpuscular volume. Additionally, there was a significant rise in neutrophils, eosinophils, cell alterations, and nuclear abnormalities percentages, along with a decrease in monocytes, coupled with a dose-dependent decrease in lymphocytes. Furthermore, only the highest dose of HA in the recovered groups continued to cause a significant increase in white blood cells. White blood cells remained lower, and the proportion of apoptotic RBCs remained higher in the high-dose group. The persistence of most of the haematological and histological disorders even after recovery period indicates a failure of physiological compensatory mechanisms to overcome the HA-associated problems or insufficient duration of recovery. Thus, these findings encourage the inclusion of this new hazardous agent in the biomonitoring program and provide a specific pattern of hematological profile in HA-challenged fish. Further experiments are highly warranted to explore other toxicological hazards of HA using dose/time window protocols.

Abstract

The joint impact of tadalafil (Cilais) as a pharmaceutical residue and microplastics on fish is not well comprehended. The current study examined haematological, biochemical, and antioxidant parameters, along with immunohistochemical and histological indications in tilapia (Oreochromis niloticus) after being exposed to tadalafil, polyethylene microplastics (PE-MPs), and their mixtures for 15 days. The fish were distributed into 1st group control group (The fish was maintained in untreated water without any supplements); 2nd group exposed to 10 mg/L PE-MPs;3rd group exposed to 20 mg/l tadalafil (Cilais); 4th group exposed to 20 mg/l tadalafil (Cilais) + 10 mg/LPE-MPs (in triplicate). The levels of creatinine, uric acid, glucose, AST, ALT, and albumin in fish treated with tadalafil alone or in combination with PE-MPs were significantly higher than those in the control group. Fish exposed to PE-MPs, tadalafil, and tadalafil plus PE-MPs showed significantly lower levels of RBCs, Hb, Ht, neutrophils, and lymphocytes compared to the control group. Serum levels of total antioxidant capacity and reduced glutathione (GSH) were notably lowered in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations in comparison to the control group. Malondialdehyde (MDA) serum levels were notably elevated in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations compared to the control group. The most severe impact was observed in the tadalafil + PE-MPs combination group. Interleukin-6 (IL-6) levels were significantly increased in liver tissues following exposure to both tadalafil and microplastics compared to tissues exposed to only one substance or the control group. Changes in the gills, liver, and renal tissues were seen following exposure to PE-MPs, tadalafil, and tadalafil + PE-MPs combination in comparison to the control group of fish. Ultimately, the mixture of tadalafil and PE-MPs resulted in the most detrimental outcomes. Tadalafil and PE-MPs exhibited showed greater adverse effects, likely due to tadalafil being absorbed onto PE-MPs.

Background

Commercial tobramycin ophthalmic solution is frequently used empirically to treat ocular disorders in equines, despite being primarily formulated for use in humans. It has been noted that tobramycin MIC90 concentration (minimal inhibitory concentration to 90% of microbial growth) rapidly declined following topical administration. It is hypothesized that adjustment of the pH of the empirically used tobramycin ophthalmic solution -prepared for human use- with the pH of the tears of donkeys, could increase the bioavailability of the drug and subsequently improve its penetration to the aqueous humor. Therefore, this study aimed to evaluate the impact of pH adjustment of the empirically used tobramycin ophthalmic solution on MIC90 concentration in tears and aqueous humor of donkeys (Equus asinus). The study was conducted on six (n = 6) clinically healthy donkeys. In each donkey, one eye was randomly selected to receive 210 µg tobramycin of the commercial tobramycin (CT) and used as a positive control (C group, n = 6). The other eye (treated eye) received 210 µg of the modified tobramycin ophthalmic solution (MT) (T group, n = 6). Tears and aqueous humor samples were collected 5-, 10-, 15-, 30- min, and 1-, 2-, 4-, and 6 h post-instillation.

Results

Modifying the pH of the empirically used commercial tobramycin ophthalmic solution in donkeys at a pH of 8.26 enhanced the drug’s bioavailability. The MIC90 of the most hazardous bacteria isolated from equines’ eyes such as Pseudomonas aeruginosa (MIC90 = 128 µg/ml) and Staphylococcus aureus (MIC90 = 256 µg/ml) was covered early (5 min post-instillation) and over a longer period in donkey tears (239–342 min) and aqueous humor (238–330 min) with the modified tobramycin solution.

Conclusions

Adjustment of the pH of the commercial tobramycin ophthalmic solution, empirically used by veterinarians to treat donkeys’ ophthalmic infections at a pH of 8.26, isotonic with the donkeys’ tears pH, resulting in higher concentrations of tobramycin in tears and aqueous humor for a longer time.

Hospitalized patients often develop acute renal failure (ARF), which causes severe morbidity and death. This research investigates the potential renoprotective benefits of sildenafil and furosemide in glycerol-induced ARF, and measures kidney function metrics in response to nanoparticle versions of these medications. Inducing ARF is commonly done by injecting 50% glycerol intramuscularly. Rats underwent a 24-h period of dehydration and starvation before slaughter for renal function testing. We investigated urine analysis, markers of oxidative stress, histology of kidney tissue, immunohistochemistry analysis of caspase-3 and interleukin-1 beta (IL-1 β), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase–associated lipocalin (NGAL), which are specific indicators of kidney tissue damage. The results of our study showed that the combination of sildenafil and furosemide, using both traditional and nanoparticle formulations, had a greater protective effect on the kidneys compared to using either drug alone. The recovery of renal tissue indicators, serum markers, and urine markers, which are indicative of organ damage, provides evidence of improvement. This was also indicated by the reduction in KIM-1 and NGAL tubular expression. The immunohistochemistry tests showed that the combination therapy, especially with the nanoforms, greatly improved the damaged cellular changes in the kidneys, as shown by higher levels of caspase-3 and IL-1β. According to the findings, a glycerol-induced rat model demonstrates that sildenafil and furosemide, either alone or in combination, in conventional or nanoparticulate forms, improve ARF dysfunction. The synergistic nanoparticulate compositions show remarkable effectiveness. This observation highlights the possible therapeutic implications for ARF treatment.

Abstract

Background

Hepatocyte death and a systemic inflammatory response are the outcome of a complex chain of events mediated by numerous inflammatory cells and chemical mediators. The point of this study was to find out if tadalafil and/or Lepidium sativum (L. sativum) could help people who have been exposed to carbon tetrachloride (CCL₄) and are experiencing acute moderate liver failure. This was especially true when the two were used together.

Method and materials

To cause mild liver failure 24 h before sacrifice, a single oral dosage of CCL₄ (2.5 mL/kg b.w.) (50% in olive oil) was utilized. Furthermore, immunohistochemical expression of nuclear factor kappa B (NF-κB) as well as histological abnormalities were performed on liver tissue.

Results

The results showed that tadalafil and/or L. sativum, especially in combination, performed well to cure acute mild liver failure caused by CCL₄. This was demonstrated by a decrease in NF-κB expression in the liver tissue and an improvement in organ damage markers observed in the blood and liver tissues. Furthermore, such therapy reduced interleukin1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in the liver tissue. It’s worth noting that the tested combination resulted in greater liver improvement.

Conclusions

According to the findings, tadalafil and L. sativum, particularly in combination, have the ability to protect the liver from the negative effects of CCL₄ exposure. Because of its capacity to improve liver function, restore redox equilibrium, and decrease inflammatory mediators, it is a prospective option for mitigating the negative effects of common environmental pollutants such as CCL₄.

This study aimed to investigate the impact of a dietary probiotic supplement on struggling behavior, immune response, and meat quality of shackled broiler chickens exposed to preslaughter stress. Two hundred and ten 1-day-old male Ross 708 broiler chicks were divided among 21 floor pens (10 chicks per pen). The pens were randomly distributed to 1 of 3 dietary treatments containing a probiotic, Bacillus subtilis, at 0 (control), 0.25 (0.25×), and 0.5 (0.5×) g/kg (n = 7). At the end of the experiment (d 35), birds were transported for a journey of 80 km to the abattoir, each crate contained 5 pen mates, 2 birds of them (2 bird per crate, total 14 birds per treatment) were randomly selected for testing. Struggling behavior measurements began after the birds had arrived at the abattoir. Serum and muscle samples (right leg and breast) were collected for immune response and meat quality parameters. The results indicated that probiotic supplemented broilers had lower breast muscle protein carbonyls and serum levels of IgM but higher breast muscle total antioxidant capacity (TAC) compared to those of controls. In addition, probiotic supplemented broilers’ leg and breast muscle had higher color lightness and greater water holding capacity (WHC%) with lower cooking loss (CL) and lower pH values (P < 0.05). Probiotic supplemented broilers’ breast and leg meat was also tastier (P < 0.05) compared to controls. There were no treatment effects on other measured parameters including struggling behavior, serum IgA and IgG concentrations, and breast muscle malondialdehyde (MDA) (P > 0.05). These results suggest that the probiotic supplement could be an alternative management tool for promoting broiler health and welfare by modifying immune response and meat quality.