scholarly journals Protective effects of fullerenol against chronic doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer

2009 ◽  
Vol 63 (3) ◽  
pp. 259-268 ◽  
Author(s):  
Rade Injac ◽  
Natasa Radic ◽  
Biljana Govedarica ◽  
Aleksandar Djordjevic ◽  
Borut Strukelj
Keyword(s):  
Colorectal Cancer ◽  
Liver Tissue ◽  
Time Span ◽  
Free Radical Scavengers ◽  
Male Rat ◽  
Antioxidant Vitamin ◽  
Protective Effects ◽  
Radical Scavengers ◽  
Derivatives Of

Since the introduction of Doxorubicin (Dox) for the treatment of cancer in 1969, this compound has demonstrated high antitumor efficacy. Dox's use in chemotherapy has been limited largely due to its diverse toxicities, including cardiac, liver, renal, pulmonary, hematological and testicular toxicity. Various attempts have been made to reduce Dox-induced toxicity. These include dosage optimization, synthesis and use of analogues. Moreover, a number of agents have been investigated as protective agents during Dox therapy. Polyhydroxilated derivatives of fullerene, named fullerenols C60(OH)n, are being extensively studied due to their great potential as antioxidants. It is proposed that they might act as free radical scavengers in biological systems, in xenobiotics-induced oxidative stress as well as against radioactive irradiation. We have investigated the effects of fullerenol C60(OH)24 (Frl) at doses of 25, 50 and 100 mg kg-1 week (for a time-span of three weeks) on heart and liver tissue after Doxorubicin (Dox)-induced toxicity in rats with colorectal cancer. In the present study, in vivo Wistar male rat model was used to explore whether Frl could protect against Dox-induced (1.5 mg/kg/week for three weeks) chronic cardio- and hepatotoxicity and compared the effect with a well-known antioxidant, vitamin C (100 mg/kg/week for three weeks). Commercially available methods were used for blood and pathohystological analysis and for the measurement of enzyme activity (SOD, MDA, GSH, GSSH, GPx, GR, CAT, CK, LDH, ?-HBDH, AST, ALT) in serum and homogenate samples of heart and liver tissues. According to macroscopic, microscopic, hematological, biochemical, physiological, pharmacological, and pharmacokinetic results, we confirmed that, at all examined doses, Frl exhibits a protective influence on the heart and liver tissue against chronic toxicity induced by Dox.

4-Substituted Coumarin Antioxidants

2019 ◽  
Vol 800 ◽  
pp. 30-35
Author(s):  
Ilze Verpakovska ◽  
Dārta Zelma Skrastiņa ◽  
Inese Mieriņa ◽  
Mara Jure
Keyword(s):  
Free Radical ◽  
Antiradical Activity ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Derivatives Of

Few derivatives of 3-arylmethyl-4-hydroxycoumarin and 4-aryl-3,4-dihydrocoumarin as potential free radical scavengers were synthesized. The antiradical activity of these compounds was measured according to 1,1-diphenyl-2-picrylhidrazyl and galvinoxyl tests. It strongly depends on phenol-type substituent attached to the coumarin skeleton, nevertheless the chromen-2-one scaffold by itself plays an important role for the antiradical activity.

scholarly journals Metabolism of a glutathione conjugate of 2-hydroxyoestradiol-17β in the adult male rat

1972 ◽  
Vol 126 (5) ◽  
pp. 1067-1071 ◽  
Author(s):  
John S. Elce
Keyword(s):  
Bile Duct ◽  
Adult Male ◽  
Analytical Techniques ◽  
Male Rats ◽  
Male Rat ◽  
Glutathione Conjugate ◽  
Before And After ◽  
Adult Male Rat ◽  
Derivatives Of

Adult male rats with cannulated or ligated bile ducts were given S-(2-hydroxyoestradiol-1-yl)[35S]glutathione, S-(2-hydroxy[6,7-3H2]oestradiol-1-yl)glutathione or S-(2-hydroxyoestradiol-1-yl)[glycine-3H]glutathione by intraperitoneal injection. The recovery of radioactivity in the bile of bile duct-cannulated rats was 33–86% and in the urine of bile duct-ligated rats was 54–105%. Oestrogen thioether derivatives of glutathione, cysteinylglycine, cysteine and N-acetylcysteine were isolated from bile; only the N-acetylcysteine derivatives could be identified in the urine. The steroid moiety was characterized by microchemical tests before and after treatment with Raney nickel: 2-hydroxyoestradiol-17β was released from the glutathione conjugate, and 2-hydroxyoestrone and 2-hydroxyoestrone 3-methyl ether from the other conjugates. From intact rats the recovery of administered radioactivity was about 15% in the urine and 5% in the faeces over a period of several days and the radioactivity appeared to be largely protein-bound. The results demonstrate that injected oestrogen–glutathione conjugate undergoes conversion into N-acetylcysteine derivatives in vivo. Oestrogen–glutathione conjugates formed in the intact rat may be excreted in an apparently non-steroidal, possibly protein-bound form, which would not be detected by current analytical techniques.

Tolerance to nitroglycerin-induced preconditioning of the endothelium: a human in vivo study

2010 ◽  
Vol 298 (2) ◽  
pp. H340-H345 ◽  
Author(s):  
Tommaso Gori ◽  
Saverio Dragoni ◽  
Giuseppe Di Stolfo ◽  
Silvia Sicuro ◽  
Andrew Liuni ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Vitamin C ◽  
Vascular Endothelium ◽  
Prolonged Exposure ◽  
Control Group ◽  
Antioxidant Vitamin ◽  
Organic Nitrates ◽  
Protective Effects ◽  
Before And After

Damage and dysfunction of the vascular endothelium critically influence clinical outcomes after ischemia and reperfusion (I/R). Brief exposure to organic nitrates can protect the vascular endothelium from I/R injury via a mechanism that is similar to ischemic preconditioning and is independent of hemodynamic changes. The clinical relevance of these protective effects clearly depends on whether they can be sustained over time. Twenty-four healthy (age 25–32) male volunteers were randomized to receive 1) transdermal nitroglycerin (GTN; 0.6 mg/h) administered for 2 h on 1 day only, 2) transdermal GTN for 2 h/day for 7 days, or 3) continuous therapy with transdermal GTN for 7 days. Eight volunteers underwent continuous GTN therapy followed by intra-arterial infusion of the antioxidant vitamin C. Finally, five additional subjects underwent no therapy and served as controls. Endothelial function measurements were performed before and after induction of I/R of the arm. I/R caused a significant blunting of the flow responses to acetylcholine in the control group ( P < 0.01 vs. before I/R). A single 2-h GTN dosage, given 24 h before I/R, prevented I/R-induced endothelial dysfunction [ P = not significant (NS) vs. before I/R], but this protective effect was completely lost after 1 wk of GTN administration 2 h/day ( P < 0.05 vs. before I/R; P = NS vs. control). In subjects who received continuous GTN, endothelial responses were blunted before I/R, and I/R did not cause further endothelial dysfunction. Finally, vitamin C normalized acetylcholine responses and prevented the loss of preconditioning associated with prolonged GTN. In a separate experimental model using isolated human endothelial cells, short-term incubation with GTN caused upregulation of heme oxygenase, an effect that was lost after prolonged GTN administration. Although a single administration of GTN is able to protect the endothelium from I/R-induced endothelial dysfunction, this protection is lost upon prolonged exposure, likely via an oxidative mechanism.

Sign in / Sign up

Export Citation Format

Share Document