the cell membrane, whereas the effective agents, DO-tocopherol and trolox, are
expected to cross the cell membrane readily. These results suggest that intracellular
target(s) may be involved in the cytotoxicity of piperine. The protective emcacy of a
lipoxygenase inhibitor against piperine-induced neurotoxicity suggests that the
lipoxygenase pathway may play a role in piperine-induced free radical generation.
In addition to the harmful effects of the free radicals formed, lipoxygenase
metabolites by themselves may provoke various kinds of cell damage (Ochi et al.
1992; Sakagami et al. 1989).
It had been reported that SOD and catalase, but not fail to protect cultured
pulmonary artery (Kachel et al. 1990) endothelial cells against amidarone-induced
injury. However, SOD and catalase prevent the generation of reactive oxygen
species and glutamate-induced neurotoxicity in cultured cerebellar granule neurons
(Gunasekar et al. 1995). This discrepancy may be due to the different sites of free
radical generation in these insulting conditions. SOD and catalase form the defense
system in the hydrophilic compartment of the cell whereas u-tocopherol is the key
membrane-bound antioxidant (Cotgreave et al. 1988). In this connection, it is also
significant that piperine, due to its high lipophilicity, may directly interact with
membrane and may facilitate lipid peroxidation resulting in neuronal injury.
Although the piperine molecule contains unsaturated double-bonds in the
side-chain which may suggest antioxidant properties, recent studies indicate that
piperine contains, if any, very (Joe and Lokesh 1994; Reddy and Lokesh 1992)
weak antioxidant and free radical scavenging activity. Indeed, piperine in a concentration range similar to that used in our study was shown to increase lipid
peroxidation (Johri et al. 1992) in isolated rat jejunum epithelial cells.
22.10 Effect on Acute Kidney Injury
Acute kidney injury (AKI) is a serious complication that may be observed in up to
5% of the hospitalized patients (Basile and Yoder 2014). A chief cause of Acute
renal injury is renal ischemia–reperfusion (IR). Renal injuries caused by ischemia–
reperfusion include oxidative stress, inflammation, and damages of tubular
epithelium and vascular endothelium (Abuelo 2007). After ischemia–reperfusion,
inflammation initiates as a consequence of cell injury, subsequent molecular
products which trigger parenchymal cells of kidney and dendritic cells (DCs),
demanding the exudation of chemokines (Chen and Nuñez 2010; Kurts et al. 2013;
Rabb et al. 2016). Renal ischemia primes to leukocyte permeation and tissue injury
progress through upregulating the adhesive molecules (including ICAM-1) in
vascular endothelium, and creating cytokines (proinflammatory), viz., interleukin-6
(IL-6), interleukin-1 (IL-1), and TNF-a in kidney (Kurts et al. 2013; Thurman
2007), Moreover, renal ischemia–reperfusion increases the amalgamation of inducible nitric oxide synthase (iNOS), enhancing the production of NO which bind
with reactive oxygen species (ROS) to form peroxynitrite (ONOO), prevents
endothelial nitric oxide synthase (eNOS), diminishes NO production in
766
N. Sachan et al.
expected to cross the cell membrane readily. These results suggest that intracellular
target(s) may be involved in the cytotoxicity of piperine. The protective emcacy of a
lipoxygenase inhibitor against piperine-induced neurotoxicity suggests that the
lipoxygenase pathway may play a role in piperine-induced free radical generation.
In addition to the harmful effects of the free radicals formed, lipoxygenase
metabolites by themselves may provoke various kinds of cell damage (Ochi et al.
1992; Sakagami et al. 1989).
It had been reported that SOD and catalase, but not fail to protect cultured
pulmonary artery (Kachel et al. 1990) endothelial cells against amidarone-induced
injury. However, SOD and catalase prevent the generation of reactive oxygen
species and glutamate-induced neurotoxicity in cultured cerebellar granule neurons
(Gunasekar et al. 1995). This discrepancy may be due to the different sites of free
radical generation in these insulting conditions. SOD and catalase form the defense
system in the hydrophilic compartment of the cell whereas u-tocopherol is the key
membrane-bound antioxidant (Cotgreave et al. 1988). In this connection, it is also
significant that piperine, due to its high lipophilicity, may directly interact with
membrane and may facilitate lipid peroxidation resulting in neuronal injury.
Although the piperine molecule contains unsaturated double-bonds in the
side-chain which may suggest antioxidant properties, recent studies indicate that
piperine contains, if any, very (Joe and Lokesh 1994; Reddy and Lokesh 1992)
weak antioxidant and free radical scavenging activity. Indeed, piperine in a concentration range similar to that used in our study was shown to increase lipid
peroxidation (Johri et al. 1992) in isolated rat jejunum epithelial cells.
22.10 Effect on Acute Kidney Injury
Acute kidney injury (AKI) is a serious complication that may be observed in up to
5% of the hospitalized patients (Basile and Yoder 2014). A chief cause of Acute
renal injury is renal ischemia–reperfusion (IR). Renal injuries caused by ischemia–
reperfusion include oxidative stress, inflammation, and damages of tubular
epithelium and vascular endothelium (Abuelo 2007). After ischemia–reperfusion,
inflammation initiates as a consequence of cell injury, subsequent molecular
products which trigger parenchymal cells of kidney and dendritic cells (DCs),
demanding the exudation of chemokines (Chen and Nuñez 2010; Kurts et al. 2013;
Rabb et al. 2016). Renal ischemia primes to leukocyte permeation and tissue injury
progress through upregulating the adhesive molecules (including ICAM-1) in
vascular endothelium, and creating cytokines (proinflammatory), viz., interleukin-6
(IL-6), interleukin-1 (IL-1), and TNF-a in kidney (Kurts et al. 2013; Thurman
2007), Moreover, renal ischemia–reperfusion increases the amalgamation of inducible nitric oxide synthase (iNOS), enhancing the production of NO which bind
with reactive oxygen species (ROS) to form peroxynitrite (ONOO), prevents
endothelial nitric oxide synthase (eNOS), diminishes NO production in
766
N. Sachan et al.