Ultrastructurural Picture of Cyclophosphamide-Induced Damage to the Liver

Abstract

We studied the ultrastructural reorganization of hepatocytes and other populations of liver cells after cyclophosphamide treatment. Single administration of cyclophosphamide was followed by significant ultrastructural changes in two major populations of liver cells (hepatocytes and sinusoidal endothelial cells). This treatment was also accompanied by reactive changes in Kupffer cells, lymphocytes, and plasma cells migrating into the spaces of Disse. Cyclophosphamide-induced spatial reorganization of hepatocytes was associated with a progressive decrease in the structural density of mitochondria, significant reduction of the smooth endoplasmic reticulum, and increase in autophagocytosis (e.g., sequestration of glycogen). Intracellular reorganization of endothelial cells was related to the following two factors: damage (necrobiosis) of some cells; and increase in metabolic processes, phagocytosis, and regenerative reactions in other cells.

Peroxisome Proliferator Activator Receptor (PPAR)-γLigand, but Not PPAR-α, Ameliorates Cyclophosphamide-Induced Oxidative Stress and Inflammation in Rat Liver

“…Our results show that the PPAR- γ agonist, PIO, but not the PPAR- α agonist, FEN, has hepatoprotective effects, through ameliorating CP-induced hepatic oxidative stress and inflammation. In the present study, CP administration caused hepatotoxicity evident by distortion of histological features and significant alteration in biochemical blood parameters indicative of liver function, which was in line with previous studies [26, 31–33]. …”

Crocin, a dietary colorant mitigates cyclophosphamide-induced organ toxicity by modulating antioxidant status and inflammatory cytokines

“…These results are in agreement with previous reports of increased production of ROS and depletion of the mitochondrial antioxidant defence system in kidney, heart, brain, liver, testis and urinary bladder . The free radicals are generated in vivo by various mechanisms, including mitochondrial dysfunction, respiratory burst and the activity of various oxidases . The possible mechanism for the free radical‐induced mitochondrial dysfunction appears to be the inactivation of respiratory‐chain enzymes, such as NADH‐cytochrome c reductase and succinate‐cytochrome c reductase, by the induction of metal‐catalysed oxidation within the active centres of the respiratory‐chain complexes.…”

The ameliorative influence of melatonin against hepatotoxicity-induced by taxol in adult rats

“…The rough endoplasmic reticulum appeared markedly fragmented into small rods, detached from the nucleus, and lost their attached ribosomes. This observation agreed with that of Lushnikova et al (2011) The fine structural observations of TXL-treated rats` hepatocytes revealed the presence of numerous lysosomes which might be participated in focal cytoplasmic degradation and in the storage or metabolism of such cytotoxic drug. In this regard, the results agreed with those obtained from Ahmed & Ghobara (2013) and Kandil et al (2021).…”