Different Cytotoxic Effects of Caper from Different Geographical Regions May Be Related to Changes in Mitochondrial Sirt3

Background and objectives: Beside its nutritional role, caper (Capparis spinosa) has long been used as an analgesic, anti-inflammatory, anti-diabetic and anti-cancer remedy. In the present study, we tested whether this plant can make effective changes in Sirt3 and mitochondrial function in colorectal carcinoma cell line since mitochondrial dysfunction has long been implicated in both cancer and diabetes and benefit confers by caper in these diseases might be due to mitochondrial alterations. Methods: Total flavonoids and phenolics were assayed using colorimetric tests. Cytotoxicity of a phenolic-flavonoid rich extract of caper collected from two different geographical regions (south and west) were mechanistically studied in HT-29 cell line. Activity of an essential mitochondrial enzyme, Sirt3 has also been evaluated along with other parameters. IC50 of extracts were determined by MTT cytotoxicity assay, cell death and mitochondrial membrane potential were evaluated via flow cytometric analysis. Also, at IC50 concentrations, Sirt3 activity was determined fluorimetrically. Results: The results showed that caper induced significant cytotoxicity in HT-29 cells followed by mitochondrial membrane potential collapse, ROS overproduction, Sirt3 activity alteration and cell death. Conclusions: The above-mentioned cytotoxic parameters were inversely proportional to the phenolic and flavonoid contents of the extract showing that other mechanisms beyond their antioxidant capacities may contribute to their anti-cancer effects. In other term, these results suggest that antioxidant capacity may not directly contribute to the anticancer property

The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

Taurine (2-aminoethane sulfonic acid) is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid) is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 µM, 100 µM and 1000 µM) of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5‑Fluorouracil, Doxorubicin and Dacarbazine) via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+). Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione) were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug‑treated livers. It was found that taurine (5 and 10 mM) and glycine (5 and 10 mM) administration significantly mitigated the biomarkers of liver injury and attenuated drug‑induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.</p

Impact of Whey Protein Edible Coating Containing Fish Gelatin Hydrolysates on Physicochemical, Microbial, and Sensory Properties of Chicken Breast Fillets

This study aims to research the impact of coatings containing whey protein (WP), fish gelatin hydrolysates (FGH), and both compounds together (WP + FGH) on the shelf-life of chicken breast fillets over the course of 16 days of cold storage (4 &deg;C, 4-day intervals), as assessed by their physicochemical, microbiological, and sensory properties. Overall, cooking loss, pH value, total volatile base nitrogen, free fatty acids, peroxide value, and thiobarbituric acid reactive substances increased with storage time in all samples. WP + FGH coated samples had significantly lower variation in all these parameters over the time of storage compared to other coated samples (WP and FGH), while these parameters increased greatly in control (uncoated) samples. WP + FGH coating also resulted in reduced bacterial counts of total mesophilic, aerobic psychrotrophic, and lactic acid bacteria compared to other coated and uncoated samples. The sensory evaluation revealed no differences in the panelists&rsquo; overall acceptance at day 0 of storage between samples. The samples were considered &ldquo;non-acceptable&rdquo; by day 8 of storage; however, WP + FGH coated samples maintained an overall higher acceptability score for the sensory attributes evaluated by the panelists. Overall, this study shows the potential of WP + FGH coatings for prolonging the shelf-life of chicken breast fillets

Propylthiouracil-induced mitochondrial dysfunction in liver and its relevance to drug-induced hepatotoxicity

Background: Propylthiouracil (PTU) administration is associated with several cases of hepatotoxicity, especially in children. The mechanism(s) of PTU-induced hepatotoxicity is obscure. In the current study, we aimed to assess the effect of PTU on hepatocytes mitochondria in different experimental models. Methods: Mice were treated with PTU (10, 20, 40, 80, and 100 mg/kg, i.p) then, the liver mitochondria were isolated and evaluated. Moreover, liver mitochondria were isolated from normal mice and incubated with increasing concentrations of PTU (10 µM-1 mM). Mitochondrial dehydrogenases activity, mitochondrial membrane potential, mitochondrial swelling, and mitochondrial adenosine triphosphate (ATP) content were monitored. Results: PTU hepatotoxicity was biochemically evident in mice by increased serum biomarkers of liver injury. PTU also caused a decrease in mitochondrial dehydrogenases activity, increased mitochondrial swelling, depleted mitochondrial ATP, and caused mitochondrial depolarization both in vitro and in vivo. Conclusion: Our data suggest mitochondrial dysfunction as a mechanism for PTU-induced hepatotoxicit

The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

Taurine (2-aminoethane sulfonic acid) is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid) is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 μM, 100 μM and 1000 μM) of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5 Fluorouracil, Doxorubicin and Dacarbazine) via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+). Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione) were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug treated livers. It was found that taurine (5 and 10 mM) and glycine (5 and 10 mM) administration significantly mitigated the biomarkers of liver injury and attenuated drug induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury

Antimalarial Drugs-Induced Hepatic Injury in Rats and the Protective Role of Carnosine

Background: Chloroquine and amodiaquine are used in the prophylaxis and treatment of malaria. However, hepatic injury is associated with malaria drug therapy. On the other hand, there is no promising hepatoprotective agent for prophylaxis or treatment of antimalarial drugs‑induced liver injury. Carnosine is a naturally occurring peptide with pleiotropic protective properties in different tissues. This investigation aimed to evaluate the effect of carnosine administration in antimalarial drugs-induced hepatic injury in rats. Methods: Animals were treated with amodiaquine (180 mg/kg, oral) or chloroquine (970 mg/kg, oral). Carnosine (250, 500 and 1000 mg/kg, i.p) was administered as the hepatoprotective agent against antimalarial drugs liver injury. Results: Liver injury was manifested biochemically by a significant increase in serum level of ALT, LDH, and AST. In addition, hepatic tissue from antimalarial drugs‐treated rats showed a significant increase in reactive oxygen species (ROS), lipid peroxidation and protein carbonylation along with a decrease in hepatic glutathione reservoirs and total antioxidant capacity. Moreover, the liver histopathologic evaluation revealed significant congestion, inflammation, and necrosis in amodiaquine and/or chloroquine-treated animals. Carnosine administration significantly alleviated antimalarial drugs-induced pathologic changes in serum biochemistry and liver tissue. Conclusion: Our data suggest that carnosine possesses protective properties against amodiaquine and/or chloroquine‑induced liver injury possibly through mitigation of drug-induced oxidative stress and its consequent events

Effect of taurine on chronic and acute liver injury: Focus on blood and brain ammonia

Hyperammonemia is associated with chronic and acute liver injury. There is no promising therapeutic agent against ammonia-induced complications. Hence, finding therapeutic molecules with safe profile of administration has clinical value. The present study was conducted to evaluate the role of taurine (TA) administration on plasma and brain ammonia and its consequent events in different models of chronic and acute liver injury and hyperammonemia. Bile duct ligated (BDL) rats were used as a model of chronic liver injury. Thioacetamide and acetaminophen-induced acute liver failure were used as acute liver injury models. A high level of ammonia was detected in blood and brain of experimental groups. An increase in brain ammonia level coincided with a decreased total locomotor activity of animals and significant changes in the biochemistry of blood and also liver tissue. TA administration (500 and 1000 mg/kg, i.p), effectively alleviated liver injury and its consequent events including rise in plasma and brain ammonia and brain edema. The data suggested that TA is not only a useful and safe agent to preserve liver function, but also prevented hyperammonemia as a deleterious consequence of acute and chronic liver injury. Keywords: Amino acid, Ammonia, Brain edema, Hepatic encephalopathy, Hepatic injury, Hepatoprotectiv