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{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc}}
{{Drugbox {{Drugbox
| verifiedrevid = 416744062 | verifiedrevid = 420155306
| IUPAC_name = (6''R'',7''R'')-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-<br>7--5-thia-1-<br>azabicyclooct-2-ene-2-carboxylate | IUPAC_name = (6''R'',7''R'')-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-<br />7--5-thia-1-<br />azabicyclooct-2-ene-2-carboxylate
| image = Cefaloridine.svg | image = Cefaloridine.svg
| width = 250 | width = 250
<!--Clinical data-->
| tradename =
| Drugs.com = {{drugs.com|international|cephaloridine}}
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⚫ | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
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<!--Pharmacokinetic data-->
⚫ | bioavailability =
⚫ | protein_bound =
⚫ | metabolism =
⚫ | elimination_half-life =
⚫ | excretion = Renal
<!--Identifiers-->
⚫ | CAS_number = 50-59-9
⚫ | ATC_prefix = J01
⚫ | ATC_suffix = DB02
⚫ | PubChem = 5773
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
⚫ | DrugBank = DB09008
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5569 | ChemSpiderID = 5569
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = LVZ1VC61HB | UNII = LVZ1VC61HB
⚫ | KEGG_Ref = {{keggcite|correct|kegg}}
| InChI = 1/C19H17N3O4S2/c23-14(9-13-5-4-8-27-13)20-15-17(24)22-16(19(25)26)12(11-28-18(15)22)10-21-6-2-1-3-7-21/h1-8,15,18H,9-11H2,(H-,20,23,25,26)/t15-,18-/m1/s1
⚫ | KEGG = D01075
⚫ | smiles = O=C2N1/C(=C(\CS12NC(=O)Cc3sccc3)C4ccccc4)C()=O
| InChIKey = CZTQZXZIADLWOZ-CRAIPNDOBC
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 316157 | ChEMBL = 316157
<!--Chemical data-->
⚫ | C=19 | H=17 | N=3 | O=4 | S=2
⚫ | smiles = O=C2N1/C(=C(\CS12NC(=O)Cc3sccc3)C4ccccc4)C()=O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C19H17N3O4S2/c23-14(9-13-5-4-8-27-13)20-15-17(24)22-16(19(25)26)12(11-28-18(15)22)10-21-6-2-1-3-7-21/h1-8,15,18H,9-11H2,(H-,20,23,25,26)/t15-,18-/m1/s1 | StdInChI = 1S/C19H17N3O4S2/c23-14(9-13-5-4-8-27-13)20-15-17(24)22-16(19(25)26)12(11-28-18(15)22)10-21-6-2-1-3-7-21/h1-8,15,18H,9-11H2,(H-,20,23,25,26)/t15-,18-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = CZTQZXZIADLWOZ-CRAIPNDOSA-N | StdInChIKey = CZTQZXZIADLWOZ-CRAIPNDOSA-N
⚫ | CAS_number = 50-59-9
| CASNo_Ref = {{cascite|correct|CAS}}
⚫ | ATC_prefix = J01
⚫ | ATC_suffix = DB02
⚫ | PubChem = 5773
⚫ | DrugBank =
⚫ | KEGG_Ref = {{keggcite|correct|kegg}}
⚫ | KEGG = D01075
⚫ | C=19|H=17|N=3|O=4|S=2
| molecular_weight = 415.486 g/mol
⚫ | bioavailability =
⚫ | protein_bound =
⚫ | metabolism =
⚫ | elimination_half-life =
⚫ | excretion = Renal
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⚫ | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
⚫ | legal_status =
⚫ | routes_of_administration =
}} }}
'''Cefaloridine''' (or '''cephaloridine''') is first generation semisynthetic derivative of ]. It is unique among cephalosporins in that it exists as a ]. '''Cephaloridine''' (or '''cefaloridine''') is a first-generation semisynthetic derivative of antibiotic ]. It is a ], like penicillin. Its chemical structure contains ],] and a ].

Cephaloridine is mainly used in veterinary practice. It is unique among cephalosporins in that it exists as a ].{{citation needed lead|date=August 2020}}


==History== ==History==
Since the discovery of cephalosporins P, N and C in 1948 there have been many studies describing the antibiotic action of cephalosporins and the possibility to synthesize derivatives. Hydrolysis of cephalosporin C, isolation of 7-aminocephalosporanic acid and the addition of side chains opened the possibility to produce various semi-synthetic cephalosporins. In 1962, ] and cephaloridine were introduced.<ref name="Mason">Mason, I.S, Kietzmann, M., Cephalosporins-pharmalogical basis of clinical use in veterinary dermatology, Veterinary Dermatology 1999, 10, 187-192</ref> Since the discovery of cephalosporins P, N and C in 1948 there have been many studies describing the antibiotic action of cephalosporins and the possibility to synthesize derivatives. Hydrolysis of cephalosporin C, isolation of 7-aminocephalosporanic acid and the addition of side chains opened the possibility to produce various semi-synthetic cephalosporins. In 1962, ] and cephaloridine were introduced.<ref name="Mason">{{cite journal |doi=10.1046/j.1365-3164.1999.00183.x |title=Cephalosporins - pharmacological basis of clinical use in veterinary dermatology |journal=Veterinary Dermatology |volume=10 |issue=3 |pages=187–92 |year=1999 | vauthors = Mason IS, Kietzmann M |pmid=34644916 }}</ref>


Cephaloridine was temporary popular because it was better tolerated intramuscular and attained in higher and more sustained levels in blood than cephalothin. However, it binds to proteins to a much lesser extent than ]. Because it is also poorly absorbed after oral administration the use of this drug for humans declined rapidly, especially since the second generation of cephalosporins was introduced in the 1970s. <ref name="Mason"/> Today it is more commonly used in veterinary practice to treat mild to severe bacterial infections caused by penicillin resistant and penicillin sensitive Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes, Streptococcus pneumoniae, Bacillus sutbtilis, Klebsiella, Clostridium diptheriae, Salmonella and Shigella.<ref>R.K. CHAUDHARY AND A.K. SRIVASTAVA, Disposition and dosage regimen of cephaloridine in calves, Vezerkny Research Communications, 13 (1989) 325-329. http://www.springerlink.com/content/l67g7035w9113317/fulltext.pdf</ref> Interest in studying cephalosporins was brought about by some unusual properties of cephaloridine. This antibiotic stands in sharp contrast to various other cephalosporins and to the structurally related penicillins in undergoing little or no net secretion by the mammalian kidney. Cephaloridine is, however, highly ] to the proximal renal tubule, the segment of the nephron responsible for the secretion of organic anions, including para-am-minohippurate (PAH), as well as the various penicillin and cephalosporin antibiotics. The cytotoxicity of cephaloridine is completely prevented by ] and several other inhibitors of organic anion transport, including the nearly nontoxic cephalosporin cephalothin.<ref>Bruce M Tune and Doris Fravert, Mechanisms of cephalosporin nephrotoxicity: A comparison of cephaloridine and cephaloglycin, Kidney International (1980) 18, 591–600; doi:10.1038/ki.1980.177 http://www.nature.com/ki/journal/v18/n5/pdf/ki1980177a.pdf</ref> Cephaloridine was briefly popular because it tolerated intramuscularly and attained higher and more sustained levels in blood than cephalothin. However, it binds to proteins to a much lesser extent than ]. Because it is also poorly absorbed after oral administration the use of this drug for humans declined rapidly, especially since the second generation of cephalosporins was introduced in the 1970s.<ref name="Mason"/> Today, it is more commonly used in veterinary practice to treat mild to severe bacterial infections caused by ] resistant and penicillin sensitive Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes, Streptococcus pneumoniae, Bacillus subtilis, Klebsiella, Clostridium diphtheriae, Salmonella and Shigella.<ref>{{cite journal | vauthors = Chaudhary RK, Srivastava AK | title = Disposition and dosage regimen of cephaloridine in calves | journal = Veterinary Research Communications | volume = 13 | issue = 4 | pages = 325–9 | year = 1989 | pmid = 2781723 | doi = 10.1007/BF00420839 | s2cid = 11295967 }}</ref> Interest in studying cephalosporins was brought about by some unusual properties of cephaloridine. This antibiotic stands in sharp contrast to various other cephalosporins and to the structurally related penicillins in undergoing little or no net secretion by the ]. Cephaloridine is, however, highly ] to the proximal renal tubule, the segment of the ] responsible for the secretion of organic anions, including para-am-minohippurate (PAH), as well as the various penicillin and cephalosporin antibiotics. The cytotoxicity of cephaloridine is completely prevented by ] and several other inhibitors of organic anion transport, including the nearly nontoxic cephalothin.<ref>{{cite journal | vauthors = Tune BM, Fravert D | title = Mechanisms of cephalosporin nephrotoxicity: a comparison of cephaloridine and cephaloglycin | journal = Kidney International | volume = 18 | issue = 5 | pages = 591–600 | date = November 1980 | pmid = 7463955 | doi = 10.1038/ki.1980.177 | doi-access = free }}</ref>


==Structure & reactivity== ==Structure & reactivity==
Cephaloridine is a cephalosporin compound with pyridinium-1-ylmethyl and 2-thienylacetamido side groups. The molecular nucleus, of which all cephalosporins are derivatives, is A3-7-aminocephalosporanic acid. Conformations around the ] are quite similar to the molecular nucleus of ], while those at the carboxyl group exocyclic to the dihydrothiazine and thiazolidine rings respectively are different.<ref>R. M. Sweet and L. F. Dahl, THE STRUCTURE OF CEPHALORIDINE HYDROCHLORIDE MONOHYDRATE, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 1969 Vol. 34, No. 1</ref> Cephaloridine is a cephalosporin compound with pyridinium-1-ylmethyl and 2-thienylacetamido side groups. The molecular nucleus, of which all cephalosporins are derivatives, is A3-7-aminocephalosporanic acid. Conformations around the ] are quite similar to the molecular nucleus of penicillin, while those at the carboxyl group exocyclic to the dihydrothiazine and thiazolidine rings respectively are different.<ref>{{cite journal | vauthors = Sweet RM, Dahl LF | title = The structure of cephaloridine hydrochloride monohydrate | journal = Biochemical and Biophysical Research Communications | volume = 34 | issue = 1 | pages = 14–6 | date = January 1969 | pmid = 5762455 | doi = 10.1016/0006-291X(69)90520-8 }}</ref>


==Synthesis== ==Synthesis==
Cephaloridine can be synthesised from Cephalotin and pyridine by deacetylation. This can be done by heating an aquous mixture of cephalotin, thiocyanate, pyridine and phosphoric acid for several hours. After cooling, diluting with water, and adjusting the pH with mineral acid, cephaloridine thiocyanate salt precipitates. This can be purified and converted to cephaloridine by pH adjustment or by interaction with ion-exchange resin.<ref>Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1120</ref> Cephaloridine can be synthesised from Cephalotin and pyridine by deacetylation. This can be done by heating an aqueous mixture of cephalotin, thiocyanate, pyridine and phosphoric acid for several hours. After cooling, diluting with water, and adjusting the pH with mineral acid, cephaloridine thiocyanate salt precipitates. This can be purified and converted to cephaloridine by pH adjustment or by interaction with ion-exchange resin.<ref>{{cite book | veditors = Osol A, Hoover JE | title = Remington's Pharmaceutical Sciences | edition = 15th | location = Easton, Pennsylvania | publisher = Mack Publishing Co. | date = 1975 | pages = 1120 }}</ref>

==Clinical use of cephaloridine==
Before the 1970s, cephaloridine was used to treat patients with urinary tract infections. Besides the drugs has been used successfully in the treatment of various lower respiratory tract infections. Cephaloridine was very effective to cure pneumococcal pneumonia. It has a high clinical and bacteriological rate of success in staphylococcal and streptococcal infections.<ref name='Owens'>{{cite book | vauthors = Owens DR | title = Advances in Pharmacology and Chemotherapy | volume = 13 | publisher = Academic Press, Inc. | pages = 83–170 }}</ref>


==Kinetics== ==Kinetics==

===Absorption=== ===Absorption===
Cephaloridine is after intramuscular injection easy absorbed and it is poorly absorbed from the gastrointestinal tract. Cephaloridine is easily absorbed after intramuscular injection and poorly absorbed from the gastrointestinal tract.<ref name='Charles'>{{cite journal | vauthors = Nightingale CH, Greene DS, Quintiliani R | title = Pharmacokinetics and clinical use of cephalosporin antibiotics | journal = Journal of Pharmaceutical Sciences | volume = 64 | issue = 12 | pages = 1899–926 | date = December 1975 | pmid = 1107514 | doi = 10.1002/jps.2600641202 }}</ref>

===Distribution=== ===Distribution===
The minor pathway of elimination is biliary excretion. When the blood serum concentration is 24µg/ml, the corresponding biliary concentration is 10µg/ml. In de spinal fluid the concentration of Cephaloridine is 6-12% of the concentration in de blood and serum. The minor pathway of elimination is biliary excretion. When the blood serum concentration is 24&nbsp;μg/mL, the corresponding biliary concentration is 10&nbsp;μg/mL. In the spinal fluid the concentration of cephaloridine is 6–12% of the concentration in the blood and serum.
Cephaloridine is distributed well into the liver, stomach wall, lung and spleen and is also found in fresh wounds one hour after injection. The concentration in the wound will decrease as the wound age increase. However, the drug is poorly penetrated into the cerebrospinal fluid and is found in a much smaller amount in the cerebral cortex. Cephaloridine is distributed well into the liver, stomach wall, lung and spleen and is also found in fresh wounds one hour after injection. The concentration in the wound will decrease as the wound age increases. However, the drug is poorly penetrated into the cerebrospinal fluid and is found in a much smaller amount in the cerebral cortex.<ref name='Charles'/>

====Pregnancy====
When cephaloridine is administered to pregnant women, the drug crosses the placenta. Cephaloridine concentrations can be measured in the serum of the newborn up to 22 hours after labor, and can reach a level of 54% of the concentration in the maternal serum. When given an intramuscular dose of 1&nbsp;g, a peak occurs in the ] after 4 hours. In ], the concentration takes about 3 hours to reach its antibacterial effect.<ref name='Owens'/>

===Metabolism and excretion===
Urine specimens showed that no other microbiologically active metabolites were present except cephaloridine and that cephaloridine is excreted unchanged.
Renal clearances were reported to be 146–280 ml/min, a plasma clearance of 167 ml/min/1,73m2 and a renal clearance of 125 ml/min/1,73m2. A serum half-life of 1,1-1,5 hour and a volume of distribution of 16 liters were reported.<ref name='Charles'/>

===Pharmacokinetics===
Pharmacokinetic analysis is not possible because appropriate data is not published. The physicochemical properties are almost the same as the other cephalosporins, therefore the pharmacokinetics are comparable.<ref name='Charles'/>


==Adverse effects== ==Adverse effects==

===Toxicity=== ===Toxicity===
Cephaloridine can cause kidney damage in humans since it is actively taken up from the blood by the proximal tubular cells via an organic anion transporter (OAT) in the basolateral membrane. Organic anions are secreted through the proximal tubular cells via unidirectional transcellular transport. The organic anions are taken up from the blood into the cells across the basolateral membrane and extruded across the brush border membrane into the tubular fluid.<ref name="Takeda">Michio Takeda, Akihiro Tojo, Takashi Sekine, Makoto Hosoyamada, Yoshikatsu Kanai and Hitoshi Endou, Role of organic anion transporter 1 (OAT1) in cephaloridine (CER)-induced nephrotoxicity, Kidney International (1999), http://www.nature.com/ki/journal/v56/n6/full/4491152a.html</ref> Cephaloridine is a substrate for OAT-1 and thus can be transported into the the proximal tubular cells, which form the renal cortex.<ref name="Timbrell">John A. Timbrell, Principles of Biochemical Toxicology, Informa Healthcare USA Inc., 2009, p 332-335</ref> Cephaloridine can cause kidney damage in humans, since it is actively taken up from the blood by the proximal tubular cells via an organic anion transporter (OAT) in the basolateral membrane. Organic anions are secreted through the proximal tubular cells via unidirectional transcellular transport. The organic anions are taken up from the blood into the cells across the basolateral membrane and extruded across the brush border membrane into the tubular fluid.<ref name="Takeda">{{cite journal | vauthors = Takeda M, Tojo A, Sekine T, Hosoyamada M, Kanai Y, Endou H | title = Role of organic anion transporter 1 (OAT1) in cephaloridine (CER)-induced nephrotoxicity | journal = Kidney International | volume = 56 | issue = 6 | pages = 2128–36 | date = December 1999 | pmid = 10594788 | doi = 10.1046/j.1523-1755.1999.00789.x | doi-access = free }}</ref> Cephaloridine is a substrate for ] and thus can be transported into the proximal tubular cells, which form the renal cortex.<ref name="Timbrell">{{cite book|last1=Timbrell|first1=John |title=Principles of Biochemical Toxicology|date=2008|publisher=CRC|location=Boca Raton, Fla.|isbn=978-0-8493-7302-2|edition=4th | pages = 332–335 }}</ref> The drugs, however, cannot move readily across the luminal membrane since it is a zwitterion. The cationic group (pyridinium ring) of the compound probably inhibits the efflux through the membrane.<ref name="Timbrell" /><ref>{{cite book|last1=Schrier|first1=Robert W.|title=Diseases of the kidney & urinary tract.|date=2007|publisher=Wolters Kluwer/Lippincott Williams & Wilkins|location=Philadelphia, PA|isbn=978-0-7817-9307-0|edition=8th | pages = 1042 | url = https://books.google.com/books?id=ERqtOZMAiw0C&q=Cephaloridine+reactivity&pg=PA1041}}</ref> This results in an accumulation of cephaloridine in the renal cortex of the kidney, causing damage and necrosis of the S2 segment of the tubule.<ref name="Takeda"/><ref name="Timbrell"/> However, there are no adverse effects on renal function if serum levels of cephaloridine are maintained between 20 and 80 μg/mL.<ref>{{cite journal | vauthors = Winchester JF, Kennedy AC | title = Absence of nephrotoxicity during cephaloridine therapy for urinary-tract infection | journal = Lancet | volume = 2 | issue = 7776 | pages = 514–6 | date = September 1972 | pmid = 4115572 | doi = 10.1016/S0140-6736(72)91908-3 }}</ref>
The drugs, however, cannot move readily across the luminal membrane since it is a zwitterion. The cationic group (pyridinium ring) of the compound probably inhibits the efflux through the membrane.<ref name="Timbrell" /> <ref>Robert W. Schrier, Diseases Of The Kidney And The Urinary Tract, Lippincott Williams & Wilkins, 2007, p 1041 http://books.google.nl/books?id=ERqtOZMAiw0C&pg=PA1041&lpg=PA1041&dq=Cephaloridine+reactivity&source=bl&ots=tZiGHvQKvZ&sig=NBOP6rdDIOHJZ0bovIuCwZBkqVQ&hl=nl&ei=mGpeTcTeLs-UOsPGyekN&sa=X&oi=book_result&ct=result&resnum=1&ved=0CBYQ6AEwADgK#v=onepage&q=Cephaloridine%20reactivity&f=false</ref> This results in an accumulation of cephaloridine in the renal cortex of the kidney, causing damage and necrosis of the S2 segment of the tubule.<ref name="Timbrell"/> <ref name="Takeda"/>


===Metabolism=== ===Metabolism===
Chephaloridine is excreted in the urine without undergoing ].<ref>Marvin Turck, Cephalosporins and Related Antibiotics: An Overview, REVIEWS OF INFECTIOUS DISEASES • VOL. 4, SUPPLEMENT • SEPTEMBER-OCTOBER 1982, © 1982 by The University of Chicago. http://cid.oxfordjournals.org/content/4/Supplement_2/S281.full.pdf</ref> Cephaloridine is excreted in the urine without undergoing ].<ref name=pmid7178754>{{cite journal | vauthors = Turck M | title = Cephalosporins and related antibiotics: an overview | journal = Reviews of Infectious Diseases | volume = 4 Suppl | pages = S281-7 | year = 1982 | pmid = 7178754 | doi = 10.1093/clinids/4.Supplement_2.S281 | jstor = 4452882 }}</ref>
It inhibits organic ion transport in the kidney. This proces is preceded by the lipid peroxidation. Therafter, probably a combination of events, such as formation of a reactive intermediate, a free radical and stimulation of lipid peroxidation, lead to peroxidative damage to cell membranes and mitochondria. It is not yet clear whether metabolic activation by cytochromes P-450, chemical rearrangements, reductive activation or all these actions are involved.<ref name="Timbrell"/> It inhibits organic ion transport in the kidney. This process is preceded by the lipid peroxidation. Thereafter, probably a combination of events, such as formation of a reactive intermediate, a free radical and stimulation of lipid peroxidation, lead to peroxidative damage to cell membranes and mitochondria. It is not yet clear whether metabolic activation by ], chemical rearrangements, reductive activation or all these actions are involved.<ref name="Timbrell"/>


The hypotheses made about the mechanism of action causing the toxiciy of cephaloridine are: The hypotheses made about the mechanism of action causing the toxicity of cephaloridine are:
* Reactive metabolites are formed by ] or emerge from destabilization of the β –lactam ring. Metabolic activation of the drugs might take place via cytochromes P-450, producing reactive metabolites. This hypothesis is formed because some inhibitors of CYTP450 decrease the toxicity and some inducers of the monooxygenases increase toxicity. It could also be possible that a reactive intermediate is formed since the β -lactam ring is unstable.<ref name="Timbrell"/> The pyridinium side-group of cephaloridine has unstable bonds to the core of the compound (in comparation with other cephalosporins). When this side-group leaves, the β –lactam ring is destabalized by intramolecular electron shifts.<ref name="Bruce">Bruce M. Tune, Nephrotoxicity of beta-lactam antibiotics: mechanisms and strategies for prevention, Pediatr Nephrol (1997) 11: 768±772, http://www.springerlink.com/content/3q23m092mlpn7rv5/</ref> Thus, the leaving group creates a reactive product. * Reactive metabolites are formed by cytochromes P-450 or emerge from destabilization of the ] ring. Metabolic activation of the drugs might take place via cytochromes P-450, producing reactive metabolites. This hypothesis is based on the behaviour of some inhibitors of CYP450, which decrease the toxicity, and some inducers of the monooxygenases which increase toxicity. It could also be possible that a reactive intermediate is formed due to the unstable β-lactam ring.<ref name="Timbrell"/> The pyridinium side-group of cephaloridine has unstable bonds to the core of the compound (in comparison with other cephalosporins). When this side-group leaves, the β-lactam ring is destabilized by intramolecular electron shifts.<ref name="Bruce">{{cite journal | vauthors = Tune BM | title = Nephrotoxicity of beta-lactam antibiotics: mechanisms and strategies for prevention | journal = Pediatric Nephrology | volume = 11 | issue = 6 | pages = 768–72 | date = December 1997 | pmid = 9438663 | doi = 10.1007/s004670050386 | s2cid = 22665680 }}</ref> Thus, the leaving group creates a reactive product.
* Both lipid peroxidation and oxidative stress can cause membrane damage. Lipid peroxidation and oxidative stress take place since lipid peroxidation products, such as malondialdehyde, have been detected. Reduced glutathione (GSH) and NADPH are both depleted. Consequently, GSSG cannot be reduced to GSH. This leads to an increased toxicity since oxidative stress cannot be reduced. In addition, nephrotoxicity is augmented by deficiency of selenium or tocopherol. The pyridinium side-group interacts with the reduced NADP in a redox cycle. It has been suggested that superoxide anion radical and hydroxyl radical may be formed and that lipid peroxidation could be responsible for the toxicity of cephaloridine.<ref name="Timbrell"/> <ref name="Bruce"/> * Both lipid peroxidation and oxidative stress can cause membrane damage. Lipid peroxidation and oxidative stress take place as lipid peroxidation products, such as malondialdehyde, have been detected. Reduced ] (GSH) and NADPH are both depleted. Consequently, GSSG cannot be reduced to GSH. This leads to an increased toxicity since oxidative stress cannot be reduced. In addition, nephrotoxicity is augmented by deficiency of ] or ]. The pyridinium side-group interacts with the reduced NADP in a redox cycle. It has been suggested that superoxide anion radicals and hydroxyl radicals may be formed and that lipid peroxidation could be responsible for the toxicity of cephaloridine.<ref name="Timbrell"/><ref name="Bruce"/>
* Damage to the mitochondria and intracellular respiratory processes and reduced mitochondrial respiration can cause nephrotoxicity. The previous mentioned damages have been detected after exposure to cephalosporins.<ref name="Timbrell"/> ] injure mitochondria by an attack on the metabolic substrate carriers of the inner membrane.<ref name="Bruce"/> Respiratory toxicity is caused by inactivation of mitochondrial anion substrate carriers.<ref name="Takeda"/> * Damage to the mitochondria and intracellular respiratory processes and reduced mitochondrial respiration can cause nephrotoxicity. The previously mentioned damages have been detected after exposure to cephalosporins.<ref name="Timbrell"/> ] injure mitochondria by an attack on the metabolic substrate carriers of the inner membrane.<ref name="Bruce"/> Respiratory toxicity is caused by inactivation of mitochondrial anion substrate carriers.<ref name="Takeda"/>


===Symptoms of kidney damage caused by cephaloridine === ===Symptoms of kidney damage caused by cephaloridine===
Some symptoms caused by cephaloridine are: asymptomatic, enzymuria, proteinuria, tubular necrosis, increased urea level in blood, anemia, increased hydrogen ion level in blood, fatigue, increased blood pressure, increased blood electrolyte level, kidney dysfunction, kidney damage, impaired body water balance and impaired electrolyte balance. <ref name="wrongdiagnosis">http://www.wrongdiagnosis.com/k/kidney_damage_cephaloridine/intro.htm</ref> Some symptoms caused by cephaloridine are: ], enzymuria, ], ], increased urea level in blood, ], increased hydrogen ion level in blood, ], increased blood pressure, increased blood electrolyte level, kidney dysfunction, kidney damage, impaired body water balance and impaired ] balance.<ref name="wrongdiagnosis">{{cite web | url = http://www.wrongdiagnosis.com/k/kidney_damage_cephaloridine/intro.htm | title = Kidney damage -- Cephaloridine | work = RightDiagnosis | publisher = Health Grades Inc }}</ref>


===Complications caused by cephaloridine=== ===Complications caused by cephaloridine===
Complications caused by the use of cephaloridine include seizures, coma, chronic kidney failure, acute kidney failure and death. <ref name="wrongdiagnosis"/> Complications caused by the use of cephaloridine include seizures, coma, chronic kidney failure, acute kidney failure and death.<ref name="wrongdiagnosis"/>


===Treatment of kidney damage caused by cephaloridine===
The damage of the kidneys can be treated by removing the toxin from the body, monitoring and supporting kidney function (dialysis if necessary) and, in severe cases, kidney transplant. Supportive therapy in the acute phase can be done by fluid, electrolyte and hypertension management. Longer term management includes monitoring of renal function, close management of high blood pressure. Furthermore, dietary management may include protein and sodium management, adequate hydration and phosphate and potassium restriction. In case of chronic ] dietary management also includes erythropoietin agonists (since anaemia is associated with chronic kidney failure), phosphate binders (in case of hyperphosphatemia), calcium supplements, Vitamin D supplements and sodium bicarbonate (to correct the acid-base disturbance).<ref name="wrongdiagnosis"/>


==References== ==References==
{{reflist|32em}}
<references/>




{{CephalosporinAntiBiotics}} {{CephalosporinAntiBiotics}}
{{Xenobiotic-sensing receptor modulators}}




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