Synergistic effect of Aminoguanidine and L-Carnosine against Thioacetamide-induced Hepatic Encephalopathy in rats: Behavioral, Biochemical and Ultra Structural Evidences, Afifi, Nehal, Ramadan Amer, Erian Emad, Sedik Ahmed, Amin Mohamed, Hassan Azza, and Saleh Dalia , 2020/07/28, Volume 99, (2020) Abstract

Hepatic encephalopathy (HE) depicts the cluster of neurological alterations that occur during acute or chronic hepatic injury. This study was aimed to evaluate the possible synergistic effect between aminoguanidine (AG; 100 mg/kg; p.o.) and l-carnosine (CAR; 100 mg/kg; p.o.) on HE that was induced by thioacetamide (TAA; 100 mg/kg; i.p) thrice weekly for six weeks. Twenty-four hours after the last treatment; behavioral changes, biochemical parameters, histopathological analysis, immunohistochemical and ultrastructural studies were conducted. Combining AG with CAR improved TAA-induced locomotor impairment and motor incoordination evidenced by; reduced locomotor activity and decline in motor skill performance as well as ameliorated cognitive deficits. Moreover, both drugs restored the levels of serum hepatic enzymes as well as serum and brain levels of ammonia. In addition to, the combination significantly modulated hepatic and brain oxidative stress biomarkers, inflammatory cytokines and cleaved caspase-3 expression. Furthermore, they succeeded to activate nuclear erythroid 2-related factor 2 (Nrf2) expression and ameliorate markers of HE including hepatic necrosis and brain astrocyte swelling. This study depicts that combining AG with CAR exerted new intervention for hepatic and brain damage in HE due to their complementary antioxidant, anti-inflammatory effect and hypoammonemic effects via Nrf2/HO-1 activation and NO inhibition.

Hepatoprotective effect of Saccharomyces Cervisciae Cell Wall Extract against thioacetamide-induced liver fibrosis in rats., El-Gendy, Zeinab A., El-Marasy Salma A., Ahmed Rania F., El-Batran Seham A., Abd El-Rahman Sahar S., Ramadan A., and Youssef S. A. H. , Heliyon, Volume 7, Issue 6, p.e07159, (2021) Abstract

Fibrosis represents a common outcome of almost all chronic liver diseases and leads to an impairment of liver function that requires medical intervention. The current study aimed to evaluate the potential anti-fibrotic effect of cell wall extract (SCCWE) against thioacetamide (TAA)-induced liver fibrosis in rats (200mg/kg b.w. i.p. twice weekly for 6 weeks) using Ursodeoxycholic acid (UDCA) as a reference anti-fibrotic product. SCCWE at two doses (50 and 100 mg/kg) significantly ameliorated the rise in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamide transferase (GGT) activities, total bilirubin and direct bilirubin, increased total protein and albumin. SCCWE significantly reduced glutathione depletion (GSH), Nitric oxide (NOx) and malondialdehyde (MDA), thioredoxin (Trx) contents and elevated nuclear factor erythroid 2-related factor 2 (Nrf-2) content. Its anti-inflammatory effects were confirmed by observing a decrease in nuclear factor-κB (NF- κβ), interleukin-1b (IL-1β) and inducible nitric oxide synthase (iNOS) content. The anti-fibrotic effects of SCCWE were explored by assessing fibrosis related markers as it significantly reduced transform growth factor-β (TGF-β) and autotaxin (ATX) contents. Administration of SCCWE significantly decreased matrix metalloproteinase-3 and 9 (MMP-3 and -9). Furthermore, it also decreased alpha smooth muscle actin (α-SMA) and caspase-3 as assessed immunohistochemically those results were similar to that of the standard drug UDCA. This study shows that SCCWE protects against TAA-induced liver fibrosis in rats, through attenuating oxidative stress, and inflammation, ameliorating MMPs, combating apoptosis and thereby fibrotic biomarkers in addition to improving histopathological changes.

Carvacrol hinders the progression of hepatic fibrosis via targeting autotaxin and thioredoxin in thioacetamide-induced liver fibrosis in rat, El-gendy, Zeinab, Ramadan A., El-Batran Seham, Ahmed R., El-Marasy Salma, Ss Abd, Abdelrahman Sahar, and Youssef S. A. H. , 2021/06/22, Volume 7, p.1 - 14, (2021) Abstract

Fibrosis is a common outcome of nearly all chronic diseases of liver that results in changes of its functions which requires medical attention. The current research aims to investigate the potential anti-fibrotic efficacy of Carvacrol against thioacetamide (TAA)-induced liver fibrosis in male rats using Ursodeoxycholic acid (UDCA) as a reference anti-fibrotic product. Carvacrol (25 and 50 mg/kg) markedly declined TAA-increased serum liver enzymes; alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) as well as total bilirubin (TB) and direct bilirubin (DB) levels as well as increased levels of total protein (TP) and albumin. Carvacrol significantly reduced glutathione depletion (GSH), Nitric oxide (NO X) and malondialdehyde (MDA) accumulation in liver tissue. Additionally, its anti-oxidant effect brightened up via affecting markers of stress found in the cell as nuclear factor erythroid 2-related factor 2 (Nrf-2) where it still had high content and decreased Thioredoxin (Trx) level. The anti-inflammatory effect of Carvacrol was confirmed by decreasing nuclear factor kappa B (NF-kB), interleukin-1beta (IL-1b) and inducible nitric oxide synthase (iNOS) contents. Carvacrol showed anti-fibrotic effect clarified by turning down fibrosis-related markers; TGF-b1, matrix metalloproteinase-3 and 9 (MMP-3 and 9) and Autotaxin (ATX) contents. Furthermore, it decreased alpha smooth muscle actin (a-SMA) and caspase-3 immune-expression. The overall outcome of aforementioned markers results showed that Carvacrol suppresses the progression of liver fibrosis via its anti-oxidant, anti-inflammatory, anti-apoptotic effect and its ability in lowering Thioredoxin and Autotaxin; hence it can be categorized as a hepatoprotective natural substance.

Bioactive Phenolics Fraction of Hedera helix L. (Common Ivy Leaf) Standardized Extract ameliorates LPS-induced Acute Lung Injury in The Mouse Model Through The Inhibition of Proinflammatory Cytokines and Oxidative Stress, Shokry, Aya, El-Shiekh Riham, Kamel Gehan, Bakr Alaa, and Ramadan Amer , 2022/05/01, p.e09477, (2022) Abstract

Hedera helix L. (family Araliaceae) is classified as a conventional plant used as a medicinal product in the cure and prevention of upper respiratory tract inflammation and infection due to its secretolytic and broncholytic effects. Our research was conducted to authenticate the anti-inflammatory effect of ivy leaves extract in the prevention of acute lung injury (ALI) caused by intranasal administration of lipopolysaccharides (LPS). In-vitro antimicrobial, anti-inflammatory, and anti-oxidant were evaluated, in addition to the in-vivo acute lung inflammation model induced by LPS in mice. The animals were divided into seven groups randomly (each group containing 10 mice): control negative (saline only), control positive (LPS group), standard (Dexamethasone 2 mg/kg), ethanolic ivy leaves extract (EIE, 100 mg/kg), ethanolic ivy leaves extract (EIE, 200 mg/kg), saponin rich fraction (SRF, 100 mg/kg) and phenolic rich fraction (PRF,100 mg/kg). Right lungs were homogenized to determine the levels of SOD, MDA, catalase, IL-10, TNF-α, NO, IL-1β, IL-6, PGE2, and MPO. Left lungs were excised for histopathology and histomorphometry. Immunohistochemistry of Cox-2 and TNF-α levels were measured. Additionally, Western blotting was used to determine the levels of phosphorylated MAPK. The data showed that the oral supplementation with EIE, 200 mg/kg significantly (P<0.05) decreased the pro-inflammatory mediators, and oxidative stress biomarkers induced by LPS. Interestingly, the phenolics showed promising activity, therefore they are responsible for the action. The ethanolic extract was also standardized through HPLC analysis for its content of rutin. In conclusion, the standardized ivy leaf extract could be advised for acute lung injury for its antimicrobial, anti-oxidant, and anti-inflammatory activities.

The pharmacological effect of apricot seeds extracts and amygdalin in experimentally induced liver damage and hepatocellular carcinoma, Ramadan, Amer, Kamel Gehan, Awad Nagwa, Shokry Aya, and Fayed Hany M. , 2020/07/01, Volume 9, (2020) Abstract

Introduction : Apricot ( Prunus armeniaca L.) has been widely used for the treatment of several disorders such as liver diseases, but the hepatoprotective and anticancer activities of its seeds were not studied before. In this study, we evaluated the pharmacological effects of apricot seeds extracts and amygdalin on prevention of liver damage and treatment of hepatocellular carcinoma. Methods : Amygdalin contents of apricot seeds in ethanolic extracts were determined using high performance liquid chromatography (HPLC) then, the ethanolic apricot seeds extract and amygdalin were evaluated for its hepatoprotective activity against carbon tetrachlorideinduced hepatotoxicity and anticancer activity against N-nitrosodiethylamine (NDEA)- induced hepatocarcinogenesis. Results : The amount of amygdalin was 5.72 g and 10.22 g/100 g extract for 70% and 99.9% ethanolic apricot seeds extracts, respectively. Pretreatment of the rats with 70% and 99.9% ethanolic apricot seeds extracts (100 mg/kg), amygdalin and silymarin (50 mg/kg) prevented elevation in liver function parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) caused by carbon tetrachloride injection with significant increase in albumin, total proteins, and no effect on total direct bilirubin when compared to those in hepatotoxic group. Both extracts also showed anticancer activity against hepatocellular carcinoma via diminishing the elevated serum levels of AST, ALT, ALP, total, direct bilirubin, albumin, total proteins, alpha-fetoprotein, malondialdehyde (MDA) and nitric oxide (NO) and elevating the decreased hepatic reduced glutathione (GSH) level when compared with NDEA- intoxicated group. Conclusion : Apricot seeds possess hepatoprotective and anticancer activities that justify its traditional use, and its potential for the treatment of liver diseases including hepatocellular carcinoma

Hepatoprotective effect of Omega-3 PUFAs against acute paracetamolinduced hepatic injury confirmed by FTIR, El-Gendy, Zeinab A., El-Batran Seham A., Youssef S. A. H., Ramadan2 A., and and Walid El Hotaby3, Rofanda M Bakeer4 Rania Ahmed1 5 F. , Human and Experimental Toxicology, (2021)
Effect of pantothenic acid on disposition kinetics and tissue residues of sulphadimidine in chickens., Ramadan, A., Hanafy MS, and Afifi N. A. , Research in veterinary science, 1992 May, Volume 52, Issue 3, p.337-41, (1992) Abstract

Sulphadimidine was administered to chickens via the intracrop route to determine plasma concentrations of the unchanged sulphonamide and its acetylated derivatives, kinetic disposition, tissue residues and acetylation. The sulphadimidine was given alone (group 1) at a dose of 200 mg kg-1 bodyweight. Pantothenic acid was given via the intracrop route at a dose of 100 mg kg-1 bodyweight one hour before (group 2) and six hours after (group 3) sulphadimidine administration (200 mg kg-1 bodyweight intracrop). The highest plasma concentrations of sulphadimidine in groups 1, 2 and 3 were reached in 1.73, 1.62 and 1.71 hours, respectively, following intracrop administration. In birds of groups 1, 2 and 3 no sulphadimidine was detected at 72, 24 and 48 hours, respectively, following its administration. Estimation of sulphadimidine in most of the body tissues revealed that all tissues examined had lower concentrations than plasma. In chickens given pantothenic acid (groups 2 and 3) before and after sulphadimidine administration, an increase in the concentration of N4 acetylated derivatives of sulphadimidine was observed compared with birds given sulphadimidine alone (group 1).

Evaluation of the safety and antioxidant activities of Crocus sativus and Propolis ethanolic extracts, Ramadan, A., Soliman G. b, Mahmoud S. S., Nofal S. M., and Abdel-Rahman RF , Journal of Saudi Chemical Society, Volume 16, Issue 1, p.13-21, (2012) Abstract

The possible toxicological effects and in vitro antioxidant activity of the ethanolic extracts of Crocus sativus and Propolis were investigated. Both extracts did not cause any mortalities or signs of toxicity in mice when administered orally at doses up to 5. g/kg. b.wt. In the sub-chronic study; the tested extracts did not produce any significant change in liver and kidney functions of rats, following oral administration for 8 successive weeks at doses of 500. mg/kg. b.wt. of each. Propolis showed remarkable in vitro antioxidant activity at concentrations of (40-100. mg/ml). In contrast, the ethanolic extract of C. sativus ethanolic extract showed weak antioxidant activity in concentrations of (1-10. mg/ml) while at concentrations of (20-100. mg/ml) failed to exhibit any antioxidant activity. It was concluded that: both extracts were non-toxic, as they did not cause any mortalities or signs of toxicity in mice when administered orally at doses up to 5. g/kg. b.wt. Daily oral administration of C. sativus, Propolis ethanolic extracts alone or in combination for 8 successive weeks to rats was quiet safe and didn't cause any toxic changes in liver and kidney. Antioxidant study showed that Propolis ethanolic extract was a more potent antioxidant than C. sativus extract. © 2010.

Effect of albendazole administration on pharmacokinetic aspects of tylosin in lactating goats., Atef, M., Ramadan A., Darwish AS, and Fahim Aisha MM , Drug metabolism letters, 2009 Aug, Volume 3, Issue 3, p.137-43, (2009) Abstract

Tylosin concentrations and its disposition kinetics in serum, urine, and milk of lactating goats following a single intravenous (i.v.) or intramuscular (i.m.) injection (10 mg kg(-1) b.wt.) were carried out using high performance liquid chromatography (HPLC).The concentration-time curve of tylosin after i.v. injection could be described by a two-compartment open model. Tylosin was rapidly distributed and eliminated from goat's bodies with t(1/2(beta)) value of 1.25 h. The V((d)) was less than one litre/kg and the MRT was 1.40 h. Concomitant administration with albendazole decreased tylosin concentrations in serum after its i.v. injection and the MRT was 1.17 h. The AUC and AUMC showed a significant decrease in goats given albendazole prior to injection as compared with those given tylosin only. Following i.m. administration, the absorption half-life and the corresponding t(max) revealed rapid absorption rate with systemic bioavailability (F%) of 76.2 %. Albendazole when given concurrently with tylosin decreased its serum concentrations due to lower bioavailability (43.25 %). Following i.v. or i.m. injection, tylosin was excreted rapidly in urine in concentration much higher than those determined in serum and milk. Tylosin administered in goats pretreated with albendazole was excreted at lower concentration in urine, with a significant decrease from 1(st) to 10(th) hours as compared with animals given tylosin only. Following i.v. or i.m. administration of tylosin, the drug was excreted in high concentrations in milk. A significant decrease in milk concentrations was reported in goats pretreated with albendazole.